1 Department of Surgery and 2 Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Acute lung injury after hemorrhagic shock
(HS) is associated with the expression of tumor necrosis factor
(TNF)- in the lung. However, the role of TNF-
and its receptors
in this pulmonary disorder remains obscure. This study examined the
temporal relationship of pulmonary TNF-
production to neutrophil
accumulation during HS and determined the role of TNF-
in neutrophil
accumulation and lung leak. HS was induced in mice by removal of 30%
of total blood volume. Lung TNF-
was measured by ELISA. Neutrophil
accumulation was detected by immunofluorescent staining, and
microvascular permeability was assessed using Evans blue dye. Although
HS induced a slight and transient increase in lung TNF-
, neutrophil
accumulation preceded the increase in TNF-
. However, lung neutrophil
accumulation and lung leak were abrogated in TNF-
knockout mice, and
both were restored by administration of recombinant TNF-
to TNF-
knockout mice before HS. Neutrophil accumulation and lung leak were
abrogated in mice lacking the p55 TNF-
receptor, but neither was
influenced by p75 TNF-
receptor knockout. This study demonstrates that a low level of pulmonary TNF-
is sufficient to mediate
HS-induced acute lung injury during HS and that the p55 TNF-
receptor plays a dominant role in regulating the pulmonary inflammatory
response to HS.
gene knockout; neutrophils; microvascular permeability; mouse; tumor necrosis factor-
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
HEMORRHAGIC SHOCK INDUCES acute lung injury manifested by neutrophil accumulation and increased microvascular permeability (1, 2). Neutrophil accumulation is a component of the pulmonary inflammatory response that contributes to increased microvascular permeability and respiratory dysfunction in a variety of lung injury models (1, 4, 9). Indeed, neutrophil depletion attenuates acute lung injury after hemorrhagic shock (1) or endotoxemia (35). Although neutrophil accumulation plays a central role in lung injury, the mechanism by which hemorrhagic shock provokes the inflammatory response remains obscure.
Hemorrhagic shock has been reported to promote pulmonary production of
proinflammatory cytokines, including tumor necrosis factor (TNF)-,
interleukin (IL)-1
, and IL-6 (5, 6, 16, 20, 34).
TNF-
induces chemokines (12, 37, 38) and adhesion molecules (11, 18, 25) in a variety of cell types and
mediates tissue injury caused by proinflammatory stimuli such as
lipopolysaccharide (LPS; see Refs. 21 and 26) and
ischemia (13). It is likely that TNF-
, serving
as a proximal mediator, provokes a pulmonary inflammatory cascade,
resulting in recruitment of neutrophils and tissue injury. However,
results of previous studies remain controversial regarding tissue
TNF-
levels after resuscitation from hemorrhagic shock (5, 14,
24, 31, 34). A number of studies have observed increased levels
of TNF-
after hemorrhagic shock (5, 24, 31, 34),
whereas others have demonstrated no change in TNF-
(14). Moreover, the temporal profile of TNF-
production
varies greatly among those studies reporting TNF-
overproduction
(5, 31, 34). These discrepancies may be the result of
different resuscitation protocols, i.e., timing, solution, and volume
used in those studies. In addition, factors induced by reperfusion of
underperfused tissues may influence tissue production and release of
proinflammatory cytokines. We have observed that unresuscitated
hemorrhagic shock induces lung neutrophil accumulation and lung injury
in mice (1, 39) and that lung injury is associated with
pulmonary expression of TNF-
(1, 2). Thus the
relationship of TNF-
to lung neutrophil accumulation and lung injury
could be determined in this model in the absence of potential
confounding factors introduced by resuscitation.
Although hemorrhagic shock induces TNF- expression in the lung, the
level of pulmonary TNF-
expression is relatively low compared with
that stimulated by bacterial LPS (1, 24). Several studies
suggest that a physiologically relevant dose of recombinant TNF-
is
insufficient to induce lung injury in naive rats or mice (30,
42). However, neutralization of TNF-
with a monoclonal antibody attenuates lung injury in a mouse model of hemorrhagic shock
(2), suggesting that endogenous TNF-
does contribute to
lung injury in the setting of hemorrhagic shock. TNF-
signaling is
mediated by two types of cell surface receptors (15). The p55 TNF-
receptor is the dominant effector in TNF-
biology and mediates most of the proinflammatory effects of TNF (25,
27-29, 38). The p75 TNF-
receptor has been found to play
an important role in ligand passing and thus enhances p55 receptor
signaling (41). The role of TNF-
in hemorrhagic
shock-induced lung neutrophil recruitment and lung injury, however,
remains to be defined, and it is unknown which TNF-
receptor is
involved. Thus determination of the role of TNF-
and its receptors
in lung neutrophil recruitment and lung injury will provide important
information regarding therapeutic suppression of the pulmonary
inflammatory response to hemorrhagic shock.
The purposes of this investigation were to examine 1) the
temporal relationship of pulmonary TNF- production to lung
neutrophil accumulation after hemorrhagic shock, 2) whether
lung neutrophil accumulation and lung injury after hemorrhagic shock
are provoked by TNF-
and, if so, 3) which TNF-
receptor mediates these effects.
![]() |
MATERIALS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Animals.
Male mice of the C57BL/6, p55 TNF- receptor knockout (p55 TNFR KO),
and p75 TNF receptor knockout (p75 TNFR KO) genotypes between the ages
of 8 and 10 wk were obtained from Jackson Laboratory (Bar Harbor, ME).
TNF-
knockout (TNF KO) mice of the same age range were generous
gifts from Dr. David Riches of the National Jewish Medical and Research
Center (Denver, CO). Mice were kept on a 12:12-h light-dark cycle with
free access to food and water. All animal experiments were approved by
the University of Colorado Health Sciences Center Animal Care and
Research Committee. During experiments, all animals received humane
care in compliance with the Guide for the Care and Use of
Laboratory Animals {Department of Health, Education, and Welfare
Publication No. [National Institutes of Health (NIH)] 85-23,
revised 1985, Office of Science and Health Reports, DRR/NIH, Bethesda,
MD 20892}.
Chemicals and reagents.
Rat monoclonal antibody to mouse neutrophil p40 antigen (clone 7/4) was
purchased from Serotec (Oxford, UK). Rat IgG and indocarbocyanine (Cy3)-conjugated donkey anti-rat IgG were purchased from Jackson ImmunoResearch Laboratories (West Grove, PA).
Fluorescein-conjugated wheat germ agglutinin was obtained from
Molecular Probes (Eugene, OR). Recombinant murine TNF- and mouse
TNF-
ELISA kits were purchased from R&D Systems (Minneapolis, MN).
Evans blue dye (EBD), LPS (Escherichia coli, 0111:B4), and
all other chemicals were obtained from Sigma (St. Louis, MO).
Experimental protocols.
The mouse hemorrhagic shock model has been described previously
(1, 39). Mice were anesthetized with inhaled
methoxyflurane. Hemorrhagic shock was induced by removing 30% of the
calculated total blood volume (0.27 ml/10 g body wt) over 60 s
through cardiac puncture. This maneuver resulted in a consistent
decrease in mean arterial pressure from 80 to 40 mmHg over a 2-h period
(data not shown). Overall mortality was <10%. No evidence of bleeding
into the pericardial space or hemothorax was found, and there were no
signs of lung or cardiac contusion. The sham procedure involved cardiac
puncture under methoxyflurane anesthesia, but no blood was removed.
Animals were killed at 0.5, 1, 2 and 4 h after blood removal.
After anesthesia and heparinization (40 mg/kg of pentobarbital sodium
and 2,000 U/kg of heparin ip), the chest was opened, and lung tissue
samples were prepared for the assessment of TNF- levels and
neutrophil accumulation. A portion of the lung tissue was embedded in
tissue-freezing medium and frozen in dry ice-chilled isopentane. The
remaining lung tissue was frozen in liquid nitrogen. All samples were
stored at
70°C before use. A separate group of animals was killed
4 h after blood removal for the assessment of lung leak.
Immunofluorescent detection of neutrophil accumulation. Lung neutrophil accumulation was determined by immunofluorescent staining as previously described (39). Tissue cryosections (5 µm thick) were prepared with a cryostat (IEC Minotome plus, Needham Heights, MA) and collected on poly-L-lysine-coated slides. All incubations were performed at room temperature. Sections were treated with a mixture of 70% acetone and 30% methanol for 5 min and then fixed with 3% paraformaldehyde for 20 min. Sections were washed with PBS, blocked with 10% normal donkey serum for 30 min, and incubated for 1 h with a monoclonal rat anti-mouse neutrophil antibody (1 µg/ml in PBS containing 1% BSA). Control sections were incubated with nonimmune rat IgG (1 µg/ml). After being washed with PBS, sections were incubated with Cy3-conjugated donkey anti-rat IgG (1:300 dilution with PBS containing 1% BSA). The cell surface was counterstained with fluorescein-conjugated wheat germ agglutinin, and the nucleus was counterstained with bis-benzimide. The sections were mounted with aqueous media. Microscopy analysis was performed with a Leica DMRXA digital microscope equipped with Slidebook software (I. I. I., Denver, CO). Neutrophils in five random fields (800 × 800 pixels or 0.017 mm2/field) were counted by a blinded viewer. Neutrophil count is expressed as mean per square millimeter.
Myeloperoxidase assay. The method for myeloperoxidase (MPO) assay has been described previously (36) with minor modifications. Tissue was homogenized in 1.0 ml of 20 mM potassium phosphate (pH 7.4) for 30 s on ice. The homogenate was centrifuged at 24,000 g for 30 min at 4°C. The pellet was resuspended and sonicated on ice for 90 s in 10 vol of hexadecyltrimethylammonium bromide buffer (0.5% hexadecyltrimethylammonium bromide in 50 mM potassium phosphate, pH 6.0). Samples were incubated in a water bath (56°C) for 2 h and then centrifuged at 5,000 g for 10 min. The supernatant was collected for assay of MPO activity as determined by measuring the H2O2-dependent oxidation of 3,3',5,5'-tetramethylbenzidine at 460 nm.
Assessment of lung leak. EBD was used to assess lung leak. EBD solution (2.5 mg/ml, 20 mg/kg body wt) was injected through a tail vein 3 h after hemorrhagic shock or sham treatment. Animals were anesthetized (40 mg/kg of pentobarbital sodium and 2,000 U/kg of heparin ip), and the chest was opened 1 h after injection of EBD. The pulmonary vasculature was flushed free of blood by gentle infusion of 10 ml of normal saline into the beating right ventricle. The lungs were then excised, weighed, and homogenized in formamide (0.5 ml/100 mg tissue). The homogenate was incubated for 18 h at 37°C and centrifuged at 10,000 g for 30 min. The supernatant was collected, and the optical density was determined spectrophotometrically at 620 nm. EBD concentration in lung homogenate was calculated against a standard curve and is expressed as micrograms of EBD per gram of tissue.
TNF- ELISA.
Lung tissue was homogenized with 4 volumes of PBS and centrifuged at
10,000 g for 20 min at 4°C. The resulting supernatant was
collected for determination of TNF-
by ELISA as previously described
(22). The detection limit for TNF-
was 5.1 pg/ml. Absorbance of standards and samples was determined
spectrophotometrically at 450 nm using a microplate reader (Bio-Rad,
Hercules, CA). Results were plotted against the linear portion of the
standard curve. TNF-
level is expressed as picograms per gram of tissue.
Statistical analysis. Data are expressed as means ± SE. An ANOVA was performed with Statview 4.0 statistical analysis software (SAS Institute, Cary, NC), and a difference was accepted as significant if the P value was smaller than 0.05 as verified by the Bonferroni-Dunn post hoc test.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Temporal recruitment of neutrophils to the lung after hemorrhagic
shock.
Lung neutrophil accumulation in wild-type mice after hemorrhagic shock
was assessed by immunofluorescent staining using a rat monoclonal
antibody to mouse neutrophils. Neutrophils were present in lungs of
sham-treated animals (Fig.
1A). Lung neutrophil count
increased after hemorrhagic shock, and neutrophils were localized in
the interstitial space adjacent to alveolar epithelial cells and in
capillaries (Fig. 1B). No immunoreactivity was detected in
negative control sections incubated with a nonimmune rat IgG (Fig.
1C). LPS induced similar neutrophil accumulation in the lung
(Fig. 1D).
|
|
Lung leak induced by hemorrhagic shock.
Lung leak was assessed in wild-type mice using the EBD assay. As shown
in Fig. 3, lung EBD concentration was
16.8 ± 1.5 µg/g in sham-treated animals, and it increased
2.5-fold to 42.8 ± 7.1 µg/g 4 h after hemorrhagic shock
(P < 0.01 vs. sham).
|
Temporal changes in lung TNF- level after hemorrhagic shock.
Hemorrhagic shock induced a slight and transient increase in lung
TNF-
in wild-type mice (Fig. 4). Lung
TNF-
was similar at different time points after sham treatment and
was 73.3 ± 17.45 pg/g wet tissue in pooled sham control. No
increase in lung TNF-
was detected 30 min after blood removal. Lung
TNF-
increased to 159.6 ± 32.9 pg/g wet tissue
(P < 0.05 vs. sham) at 1 h and returned to the
level of sham control 2 h after blood removal. In contrast, a
sublethal dose of LPS induced a dramatic increase in lung TNF-
in
wild-type mice (2,979 ± 992 pg/g wet tissue, P < 0.01 vs. saline control and hemorrhaged 1 h). TNF-
was not detectable in the lungs of TNF KO mice after LPS administration (Fig.
4).
|
Effects of TNF KO on pulmonary recruitment of neutrophils and lung
leak.
To determine the role of TNF- in lung neutrophil recruitment after
hemorrhagic shock, we examined neutrophil count in lungs of TNF KO mice
4 h after blood removal or sham treatment. Although TNF KO did not
influence lung neutrophil count after sham treatment, lung neutrophil
count was greatly reduced after hemorrhagic shock in mice lacking
TNF-
compared with that of wild-type animals (Fig.
5). Intravenous administration of a small
dose of recombinant murine TNF-
to TNF KO mice immediately before
blood removal restored lung neutrophil recruitment, although this dose
of TNF-
had a minimal influence on lung neutrophil count after sham
treatment (Fig. 5). At 30 min after hemorrhagic shock, lung neutrophil
count of TNF KO mice was 187 ± 39.0/mm2
(n = 3). This value was also significantly
lower than that of wild-type animals (385 ± 46.7/mm2)
at the same time point after hemorrhagic shock (P < 0.05).
|
|
Effects of TNFR KO on pulmonary recruitment of neutrophils and lung
leak.
To determine which TNF receptor mediates hemorrhagic shock-induced lung
neutrophil recruitment and lung injury, we subjected p55 TNFR KO and
p75 TNFR KO mice to hemorrhagic shock or sham treatment. Lung
neutrophil count after sham treatment was not influenced by either p55
TNFR KO or p75 TNFR KO (Fig. 7). However, lung neutrophil count in mice lacking the p55 TNF- receptor was greatly reduced (P < 0.01 vs. wild type) 4 h
after hemorrhagic shock and was comparable to that of mice lacking
TNF-
. In contrast, the absence of the p75 TNF-
receptor had no
influence on hemorrhagic shock-induced lung neutrophil recruitment
(Fig. 7).
|
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
In this study, we found that hemorrhagic shock induced a transient
increase in lung TNF- production and a time-dependent lung
neutrophil accumulation associated with lung leak in wild-type mice.
Lung neutrophil accumulation appeared before an increase in lung
TNF-
level. Despite this temporal discordance, TNF KO mice exhibited
attenuated lung neutrophil accumulation and lung leak after hemorrhagic
shock, and both lung neutrophil accumulation and lung leak were
restored in TNF KO mice by administration of recombinant murine TNF-
before hemorrhage. Moreover, lung neutrophil accumulation and lung leak
induced by hemorrhagic shock were similarly attenuated in mice lacking
the p55 TNF-
receptor, whereas knockout of the p75 TNF-
receptor
had no influence on either lung neutrophil accumulation or lung leak.
These results suggest that TNF-
provokes the pulmonary inflammatory
response to hemorrhagic shock and that the p55 TNF-
receptor
mediates the proinflammatory effect of TNF-
in the lung after
hemorrhagic shock.
Neutrophils are the major cellular elements involved in acute lung
inflammation after resuscitated hemorrhagic shock (32, 45). Our recent studies in a murine model found that neutrophil accumulation and tissue injury occur in the lung during hemorrhagic shock without resuscitation (1, 39) and that neutrophil
depletion attenuates acute lung injury in this model of hemorrhagic
shock (1). Thus pulmonary neutrophil recruitment is an
important factor contributing to acute lung injury regardless of
reperfusion. Although neutrophil accumulation plays a central role in
acute lung injury, the factor that provokes the pulmonary inflammatory response to hemorrhagic shock remains to be defined. TNF- is a
proinflammatory cytokine and induces chemokines and adhesion molecules
in a variety of cell types (18, 19). Previous studies demonstrated that a large dose (200 ng/g body wt or greater) of recombinant TNF-
can induce lung neutrophil accumulation and lung
injury (17, 42). Indeed, hemorrhagic shock induces
pulmonary expression of TNF-
(1, 3), and neutralization
of TNF-
with a monoclonal antibody attenuates lung injury after
hemorrhagic shock (2). These studies suggest that
endogenous TNF-
contributes to hemorrhagic shock-induced lung
injury. It remains unclear, however, whether TNF-
provokes lung
neutrophil recruitment.
In the present study, lung neutrophil count was elevated significantly
at 30 min and continued to increase for 4 h, whereas the twofold
increase in the lung TNF- level did not occur until 1 h after
hemorrhagic shock. The temporal discordance between pulmonary
neutrophil recruitment and the increase in lung TNF-
level implies
that the initial pulmonary neutrophil recruitment after hemorrhagic
shock does not require an increase in lung TNF-
production. It is
possible that a basal level of lung TNF-
is sufficient to mediate
the pulmonary inflammatory response to hemorrhagic shock.
Alternatively, some other factor(s) is responsible for the initial
pulmonary neutrophil recruitment. A slight increase in lung TNF-
level at 1 h is associated with a further accumulation of
neutrophils between 1 and 4 h. However, lung TNF-
level does not correlate with the magnitude of neutrophil accumulation, since LPS-induced lung neutrophil accumulation was comparable to that of
hemorrhagic shock, but it induced an 80-fold increase in lung TNF-
.
Together these data do not appear to support the hypothesis that
TNF-
is an important factor in hemorrhage-induced lung neutrophil recruitment.
Unexpectedly, pulmonary neutrophil accumulation 4 h after
hemorrhagic shock was greatly reduced in mice lacking TNF- compared with wild-type mice, although TNF KO had no influence on lung neutrophils after sham treatment. Moreover, lung neutrophil count was
also significantly lower in TNF KO mice at 30 min after hemorrhage, a
time point before the slight increase in lung TNF-
in wild-type mice. These results suggest that a low level of endogenous TNF-
is
required for the initiation of the pulmonary inflammatory response. Similarly, lack of endogenous TNF-
production also significantly attenuated lung leak after hemorrhage. Thus TNF-
mediates
hemorrhage-induced lung neutrophil accumulation and lung leak, although
lung TNF-
remains at a low level after hemorrhagic shock.
To further determine the role of TNF- in provoking neutrophil
accumulation and tissue injury during hemorrhagic shock, we administered a small dose of recombinant murine TNF-
(80 pg/g body
wt iv) to TNF KO mice before subjecting them to hemorrhagic shock.
Assuming that exogenously administered TNF-
distributes evenly
throughout the body, this dose of TNF-
would result in tissue
TNF-
levels comparable to that in lungs of sham-treated wild-type
mice. The hyporesponsiveness to hemorrhagic shock in TNF KO mice was
reversed by administration of recombinant TNF-
, although this dose
of TNF-
was insufficient to induce significant lung neutrophil
accumulation or lung leak in the absence of hemorrhagic shock. Together
these results demonstrate that a low level of TNF-
is required for
hemorrhagic shock to provoke acute pulmonary inflammation and injury.
Because exogenous TNF at the dose used in the present study failed to
induce a significant effect in sham-treated TNF KO animals, TNF must
synergize with some other factor(s) produced after hemorrhage to have
an effect. In this regard, TNF-
has been shown to synergize with
other proinflammatory cytokines in inducing myocardial injury
(8). It appears that both TNF-
and the unknown
factor(s) need to be present to mediate the pulmonary effect of
hemorrhagic shock. The factor(s) that TNF-
may synergize with is not
present in TNF KO animals treated with TNF-
and the sham procedure,
and TNF-
is not present in TNF KO animals treated with hemorrhagic
shock. Thus lung neutrophil accumulation and lung leak would not occur.
Lung neutrophil accumulation and lung leak occur after hemorrhage in
wild-type animals and TNF KO mice treated with recombinant TNF-
,
since both TNF-
and the factor(s) that TNF-
synergizes with are
present. Nevertheless, the factor(s) that TNF-
synergizes with to
mediate lung injury after hemorrhage shock remains to be determined.
TNF- signaling is mediated by two types of cell surface receptors,
the p55 TNF-
receptor and the p75 TNF-
receptor
(15). The p55 TNF-
receptor is the dominant effector in
TNF-
biology and mediates most of the proinflammatory effects of
TNF-
(25, 27, 28, 38). The p75 TNF-
receptor has
been found to play an important role in ligand passing and thus
enhances p55 receptor signaling (41). Indeed, lung
neutrophil infiltration in response to systemic TNF-
requires p55
TNF-
receptor signaling (25). Although the role of
TNF-
receptors in pulmonary recruitment of neutrophils and tissue
injury remains to be defined, both p55 and p75 TNF-
receptors have
been reported to be involved in neutrophil recruitment in response to
LPS (43). In the present study, mice lacking the p55
TNF-
receptor exhibited reduced lung neutrophil accumulation and
attenuated lung injury after hemorrhagic shock, and the effects of TNF
KO were mimicked by p55 TNFR KO. In contrast, absence of the p75
TNF-
receptor had no influence on either lung neutrophil
accumulation or lung injury. These results provide in vivo evidence
that the p55 TNF-
receptor mediates lung neutrophil accumulation and
acute lung injury in hemorrhagic shock. It is likely that TNF-
serves as a proximal mediator to initiate a pulmonary inflammatory
cascade during hemorrhagic shock, resulting in recruitment of
neutrophils and tissue injury, and that the p55 TNF-
receptor plays
a critical role in this process. The results of the present study
suggest that antagonization of p55 TNF-
receptor may be a
therapeutic approach for protection of the lung against hemorrhagic
shock-induced injury.
TNF- has been demonstrated to induce factors involved in tissue
neutrophil accumulation, such as chemokines (12, 37, 38),
integrins (40), and adhesion molecules (11, 18,
25). Studies using animal models of LPS-induced lung injury
suggest that TNF-
serves to signal the expression of adhesion
molecules and chemokines (10). Thereafter, lung injury
occurs as the result of the release of reactive oxygen species and
proteases from sequestered intrapulmonary neutrophils (7, 33,
44). Although resuscitation after hemorrhagic shock induces lung
intercellular adhesion molecule (ICAM)-1 expression, our previous work
has suggested that pulmonary neutrophil recruitment occurs during
unresuscitated hemorrhagic shock independent of lung ICAM-1 expression,
since lung ICAM-1 levels were unchanged and pulmonary neutrophil
recruitment was not affected in ICAM-1 knockout mice (39).
The results of the present study suggest a role for TNF-
and the p55
TNF receptor in mediating lung neutrophil accumulation and lung injury
after hemorrhagic shock. The downstream mediators of this phenomenon, however, remain to be determined.
![]() |
ACKNOWLEDGEMENTS |
---|
This work was supported in part by the National Institute of General Medical Sciences Grant GM-08315.
![]() |
FOOTNOTES |
---|
Address for reprint requests and other correspondence: X. Meng, Dept. of Surgery, Box C-320, Univ. of Colorado Health Sciences Center, 4200 E. 9th Ave., Denver, CO 80262 (E-mail: xianzhong.meng{at}uchsc.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 2 February 2001; accepted in final form 10 April 2001.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Abraham, E,
Carmody A,
Shenkar R,
and
Arcaroli J.
Neutrophils as early immunologic effectors in hemorrhage- or endotoxemia-induced acute lung injury.
Am J Physiol Lung Cell Mol Physiol
279:
L1137-L1145,
2000
2.
Abraham, E,
Jesmok G,
Tuder R,
Allbee J,
and
Chang Y.
Contribution of tumor necrosis factor- to pulmonary cytokine expression and lung injury after hemorrhage and resuscitation.
Crit Care Med
23:
1319-1326,
1995[ISI][Medline].
3.
Abraham, E,
Wunderink R,
Silverman H,
Perl TM,
Nasraway S,
Levy H,
Bone R,
Wenzel RP,
Balk R,
Allred R,
Pennington JE,
and
Wherry JC.
Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome.
J Am Med Assoc
273:
934-941,
1995[Abstract].
4.
Anderson, BO,
Brown JM,
and
Harken AH.
Mechanisms of neutrophil-mediated tissue injury.
J Surg Res
51:
170-179,
1991[ISI][Medline].
5.
Ayala, A,
Perrin MM,
Meldrum DR,
Ertel W,
and
Chaudry IH.
Hemorrhage induces an increase in serum TNF which is not associated with elevated levels of endotoxin.
Cytokine
2:
170-174,
1990[Medline].
6.
Ayala, A,
Wang P,
Ba ZF,
Perrin MM,
Ertel W,
and
Chaudry IH.
Differential alterations in plasma IL-6 and TNF levels after trauma and hemorrhage.
Am J Physiol Regulatory Integrative Comp Physiol
260:
R167-R171,
1991
7.
Barnett, CC, Jr,
Moore EE,
Mierau GW,
Partrick DA,
Biffl WL,
Elzi DJ,
and
Silliman CC.
ICAM-1-CD18 interaction mediates neutrophil cytotoxicity through protease release.
Am J Physiol Cell Physiol
274:
C1634-C1644,
1998
8.
Cain, BS,
Meldrum DR,
Dinarello CA,
Meng X,
Joo K,
Banerjee A,
and
Harken AH.
TNF- and IL-1
synergistically depress human myocardial function.
Crit Care Med
27:
1309-1318,
1999[ISI][Medline].
9.
Chignard, M,
and
Balloy V.
Neutrophil recruitment and increased permeability during acute lung injury induced by lipopolysaccharide.
Am J Physiol Lung Cell Mol Physiol
279:
L1083-L1090,
2000
10.
Cirelli, RA,
Carey LA,
Fisher JK,
Rosolia DL,
Elsasser TH,
Caperna TJ,
Gee MH,
and
Albertine KH.
Endotoxin infusion in anesthetized sheep is associated with intrapulmonary sequestration of leukocytes that immunohistochemically express tumor necrosis factor-alpha.
J Leukoc Biol
57:
820-826,
1995[Abstract].
11.
Colletti, LM,
Cortis A,
Lukacs N,
Kunkel SL,
Green M,
and
Strieter RM.
Tumor necrosis factor up-regulates intercellular adhesion molecule 1, which is important in the neutrophil-dependent lung and liver injury associated with hepatic ischemia and reperfusion in the rat.
Shock
10:
182-191,
1998[ISI][Medline].
12.
Czermak, BJ,
Sarma V,
Bless NM,
Schmal H,
Friedl HP,
and
Ward PA.
In vitro and in vivo dependency of chemokine generation on C5a and TNF-alpha.
J Immunol
162:
2321-2325,
1999
13.
Donnahoo, KK,
Meng X,
Ayala A,
Cain MP,
Harken AH,
and
Meldrum DR.
Early kidney TNF-alpha expression mediates neutrophil infiltration and injury after renal ischemia-reperfusion.
Am J Physiol Regulatory Integrative Comp Physiol
277:
R922-R929,
1999
14.
Foex, BA,
Quinn JV,
Little RA,
Shelly MP,
and
Slotman GJ.
Differences in eicosanoid and cytokine production between injury/hemorrhage and bacteremic shock in the pig.
Shock
8:
276-283,
1997[ISI][Medline].
15.
Goeddel, DV.
Signal transduction by tumor necrosis factor.
Chest
116:
69S-73S,
1999
16.
Hierholzer, C,
Kalff JC,
Omert L,
Tsukada K,
Loeffert JE,
Watkins SC,
Billiar TR,
and
Tweardy DJ.
Interleukin-6 production in hemorrhagic shock is accompanied by neutrophil recruitment and lung injury.
Am J Physiol Lung Cell Mol Physiol
275:
L611-L621,
1998
17.
Kettelhut, IC,
Fiers W,
and
Goldberg AL.
The toxic effects of tumor necrosis factor in vivo and their prevention by cyclooxygenase inhibitors.
Proc Natl Acad Sci USA
84:
4273-4277,
1987[Abstract].
18.
Krunkosky, TM,
Fisher BM,
Martin LD,
Jones N,
Akley NJ,
and
Adler KB.
Effects of TNF- on expression of ICAM-1 in human airway epithelial cells in vitro. Signaling pathways controlling surface and gene expression.
Am J Respir Cell Mol Biol
22:
685-692,
2000
19.
Luster, AD.
Chemokineschemotactic cytokines that mediate inflammation.
N Engl J Med
338:
436-445,
1998
20.
Marty, C,
Misset B,
Tamion F,
Fitting C,
Carlet J,
and
Cavaillon JM.
Circulating interleukin-8 concentration in patients with multiple organ failure of septic and nonseptic origin.
Crit Care Med
22:
673-679,
1994[ISI][Medline].
21.
Meng, X,
Ao L,
Meldrum DR,
Cain BS,
Shames BD,
Selzman CH,
Banerjee A,
and
Harken AH.
TNF- and myocardial depression in endotoxemic rats: temporal discordance of an obligatory relationship.
Am J Physiol Regulatory Integrative Comp Physiol
275:
R502-R508,
1998
22.
Meng, X,
Banerjee A,
Ao L,
Meldrum DR,
Cain BS,
Shames BD,
and
Harken AH.
Inhibition of myocardial TNF- production by heat shock: a potential mechanism of stress-induced cardioprotection against postischemic dysfunction.
Ann NY Acad Sci
874:
69-82,
1999
23.
Meng, X,
Brown JM,
Ao L,
Nordeen SK,
Franklin W,
Harken AH,
and
Banerjee A.
Endotoxin induces cardiac heat shock protein 70 and resistance to endotoxemic myocardial dysfunction.
Am J Physiol Cell Physiol
271:
C1316-C1324,
1996
24.
Molina, PE,
and
Abumrad NN.
Central sympathetic modulation of tissue cytokine response to hemorrhage.
Neuroimmunomodulation
6:
193-200,
1999[ISI][Medline].
25.
Neumann, B,
Machleidt T,
Lifka A,
Pfeffer K,
Vestweber D,
Mak TW,
Holzmann B,
and
Kronke M.
Crucial role of 55-kilodalton TNF receptor in TNF-induced adhesion molecule expression and leukocyte organ infiltration.
J Immunol
156:
1587-1593,
1996[Abstract].
26.
Nowak, M,
Gaines GC,
Rosenberg J,
Minter R,
Bahjat FR,
Rectenwald J,
MacKay SL,
Edwards CK,
and
Moldawer LL.
LPS-induced liver injury in D-galactosamine-sensitized mice requires secreted TNF- and the TNF-p55 receptor.
Am J Physiol Regulatory Integrative Comp Physiol
278:
R1202-R1209,
2000
27.
Peschon, JJ,
Torrance DS,
Stocking KL,
Glaccum MB,
Otten C,
Willis CR,
Charrier K,
Morrisey PJ,
Ware CB,
and
Mohler KM.
TNF receptor-deficient mice reveal divergent for p55 and p75 in several models of inflammation.
J Immunol
160:
943-952,
1998
28.
Pfeffer, K,
Matsuyama T,
Kundig TM,
Wakeham A,
Kishihara K,
Shahinian A,
Weigmann K,
Ohashi PS,
Kronke M,
and
Mak TW.
Mice deficient for the 55 kD tumor necrosis factor receptor are resistant to endotoxic shock yet succumb to L. monocytogenes infection.
Cell
73:
457-467,
1993[ISI][Medline].
29.
Poll, TVD,
Jansen PM,
Zee KJV,
Welborn MB,
Jong ID,
Hack CE,
Loetscher H,
Lesslauer W,
Lowry SF,
and
Moldawer LL.
Tumor necrosis factor-alpha induces activation of coagulation and fibrinolysis in baboons through an exclusive effect on the p55 receptor.
Blood
88:
922-927,
1996
30.
Remick, DG,
Kunkel RC,
and
Larrick JW.
Acute in vivo effects of human recombinant tumor necrosis factor.
Lab Invest
56:
583-590,
1987[ISI][Medline].
31.
Rhee, P,
Waxman K,
Clark L,
Kaupke CJ,
Vaziri ND,
Tominaga G,
and
Scannell G.
Tumor necrosis factor and monocytes are released during hemorrhage shock.
Resuscitation
25:
249-255,
1993[ISI][Medline].
32.
Rizoli, SB,
Kapus A,
Fan J,
Li YH,
Marshall JC,
and
Rotstein OD.
Immunomodulatory effects of hypertonic resuscitation on the development of lung inflammation following hemorrhagic shock.
J Immunol
161:
6288-6296,
1998
33.
Shanley, TP,
Warner RL,
and
Ward PA.
The role of cytokines and adhesion molecules in the development of inflammatory injury.
Mol Med Today
1:
40-45,
1995[ISI][Medline].
34.
Shenkar, R,
Coulson WF,
and
Abraham E.
Hemorrhage and resuscitation induce alterations in cytokine expression and the development of acute lung injury.
Am J Respir Cell Mol Biol
10:
290-297,
1994[Abstract].
35.
Sheridan, BC,
McIntyre RC,
Agrafojo J,
Meldrum DR,
Meng X,
and
Fullerton DA.
Neutrophil depletion attenuates dysfunction of cGMP-mediated pulmonary vasorelaxation in endotoxin-induced acute lung injury.
Am J Physiol Lung Cell Mol Physiol
271:
L820-L828,
1996
36.
Sheridan, BC,
McIntyre RCJ,
Meldrum DR,
and
Fullerton DA.
L-Arginine prevents lung neutrophil accumulation and preserves pulmonary endothelial function after endotoxin.
Am J Physiol Lung Cell Mol Physiol
274:
L337-L342,
1998
37.
Simeonova, PP,
Leonard S,
Flood L,
Shi X,
and
Luster MI.
Redox-dependent regulation of interleukin-8 by tumor necrosis factor-alpha in lung epithelial cells.
Lab Invest
79:
1027-1037,
1999[ISI][Medline].
38.
Skerrett, SJ,
Martin TR,
Chi EY,
Peschon JJ,
Mohler KM,
and
Wilson CB.
Role of the type 1 TNF receptor in lung inflammation after inhalation of endotoxin or Pseudomonas aeruginosa.
Am J Physiol Lung Cell Mol Physiol
276:
L715-L727,
1999
39.
Song Y, Ao L, Calkins CM, Raeburn CD, Harken AH, and Meng X. Differential cardiopulmonary recruitment of neutrophils during
hemorrhagic shock: a role for ICAM-1? Shock In
press.
40.
Tang, WW,
Yi ES,
Remick DG,
Wittwer A,
Yin S,
Qi M,
and
Ulich TR.
Intratracheal injection of endotoxin and cytokines. IX. Contribution of CD11a/ICAM-1 to neutrophil emigration.
Am J Physiol Lung Cell Mol Physiol
269:
L653-L659,
1995
41.
Tartaglia, LA,
Pennica D,
and
Goeddel DV.
Ligand passing: the 75-kDa tumor necrosis factor (TNF) receptor recruits TNF for signaling by the 55-kDa TNF receptor.
J Biol Chem
268:
9292-9296,
1993.
42.
Tracey, KJ,
Beutler B,
Lowry SF,
Merryweather J,
Wolpe S,
Milsark IW,
Hariri RJ,
Fahey TJ,
Zentella A,
Albert JD,
Shires GT,
and
Cerami A.
Shock and tissue injury induced by recombinant human cachectin.
Science
234:
470-474,
1986[ISI][Medline].
43.
Ulich, TR,
Yi ES,
Smith C,
and
Remick D.
Intratracheal administration of endotoxin and cytokines VII. The soluble interleukin-1 receptor and the soluble tumor necrosis factor receptor II (p80) inhibit acute inflammation.
Clin Immunol Immunopathol
72:
137-140,
1994[ISI][Medline].
44.
Wagner, JG,
and
Roth RA.
Neutrophil migration during endotoxemia.
J Leukoc Biol
66:
10-24,
1999[Abstract].
45.
Younger, JG,
Taqi AS,
Jost PF,
Till GO,
Johnson KJ,
Stern SA,
and
Hirschl RB.
The pattern of early lung parenchymal and air space injury following acute blood loss.
Acad Emerg Med
5:
659-665,
1998[Abstract].