We hypothesized that the antibody
neutralization of L-selectin would decrease the pulmonary abnormalities
characteristic of burn and smoke inhalation injury. Three groups of
sheep (n = 18) were prepared and randomized: the
LAM-(1-3) group (n = 6) was injected
intravenously with 1 mg/kg of leukocyte adhesion molecule (LAM)-(1-3)
(mouse monoclonal antibody against L-selectin) 1 h after the
injury, the control group (n = 6) was not injured or treated, and the nontreatment group (n = 6) was injured
but not treated. All animals were mechanically ventilated during the
48-h experimental period. The ratio of arterial
PO2 to inspired O2 fraction
decreased in the LAM-(1-3) and nontreatment groups.
Lung lymph flow and pulmonary microvascular permeability were elevated after injury. This elevation was significantly reduced when
LAM-(1-3) was administered 1 h after injury.
Nitrate/nitrite (NOx) amounts in plasma and lung
lymph increased significantly after the combined injury. These changes
were attenuated by posttreatment with LAM-(1-3).
These results suggest that the changes in pulmonary transvascular fluid
flux result from injury of lung endothelium by polymorphonuclear
leukocytes. In conclusion, posttreatment with the antibody for
L-selectin improved lung lymph flow and permeability index. L-selectin
appears to be principally involved in the increased pulmonary
transvascular fluid flux observed with burn/smoke insult. L-selectin
may be a useful target in the treatment of acute lung injury after burn
and smoke inhalation.
 |
INTRODUCTION |
POLYMORPHONUCLEAR
LEUKOCYTES (PMNs) play an important role in the inflammatory
processes of thermal burn and smoke inhalation injury. Endothelial
damage by these activated cells is believed to increase microvascular
permeability and edema. The selectin family of adhesion-promoting
molecules, including L-selectin, appears to be involved in the early
events of the acute inflammatory process (11). These
molecules mediate initial contact between PMNs and endothelial cells,
resulting in a "rolling" phenomenon, in which the leukocytes adhere
intermittently to the endothelial cells.
We previously investigated the effect of anti-L-selectin antibody
[leukocyte adhesion molecule (LAM)-(1-3)] 1 h
before burn and smoke inhalation injury (13). The results
showed that pretreatment with LAM-(1-3) inhibited the
increase in lung lymph flow and permeability index. Although L-selectin
contributed to the pathogenesis of acute lung injury after burn and
smoke, our previous study was not designed to answer whether
anti-L-selectin could be used therapeutically. Therefore, in the
present study, we tested the effect of posttreatment LAM-(1-3) in burn and smoke inhalation in sheep.
 |
MATERIALS AND METHODS |
The experimental procedures were approved by the Animal Care and
Use Committee of The University of Texas Medical Branch. During the
course of the experiment, the guidelines for care and use of
experimental animals, as established by the National Institutes of
Health and the American Physiological Society, were strictly observed.
Antibody modification and flow cytometry.
Purified LAM-(1-3) (14), a murine
monoclonal anti-human L-selectin antibody that interferes with PMN
attachment to human umbilical vein endothelial cells, was obtained from
Abgenix (Foster City, CA). The whole antibody caused release of
L-selectin from the surface of ovine PMNs. Therefore,
F(ab')2 fragments were prepared from the whole antibody by
pepsin digestion, as previously described (13). This
antibody blocks L-selectin function in ovine neutrophils (13). Each lot of antibody was tested by the
Limulus assay and was free of endotoxin. Interaction of this
antibody with ovine blood PMNs was measured using flow cytometry.
Leukocytes were washed and resuspended in PBS supplemented with 1%
newborn bovine serum (Flow Laboratories, McLean, VA) before incubation
with antibody at a concentration of 40 µg/ml of cell suspension
(0.4-1.0 × 106 cells) for 20 min at 4°C. The
cells were then washed in PBS and fixed in 1% paraformaldehyde.
Single-color flow cytometry was performed using FACScan
(Becton-Dickinson, Mountain View, CA). An electronic gate was set on
the neutrophil populations on the basis of forward-angle vs.
right-angle light scatter. All analyses were simultaneously run with a
mouse isotype control. Analyses were conducted with the LYSIS II
program. Becton-Dickinson CaliBRITE bands were run before each analysis
to monitor instrument performance and to set detector levels for
fluorescein isothiocyanate.
To test the nonspecific effects of the antibody, we injected
LAM-(1-3) into healthy normal sheep and monitored the
hemodynamic and blood gas changes. No obvious changes were observed in
hemodynamic parameters or blood gases.
Surgical preparation.
Eighteen female sheep [35.9 ± 1.2 (SE) kg] were surgically
prepared for chronic study under halothane anesthesia. The right femoral artery and vein were cannulated with Silastic catheters (16 gauge, 24 in.; Intracath, Becton-Dickinson Vascular Access, Sandy, UT).
A thermodilution catheter (Swan Ganz model 131F7, Baxter, Edwards
Critical-Care Division, Irvine, CA) was introduced through the right
external jugular vein into the pulmonary artery. Another catheter
(0.062 in. ID, 0.125 in. OD; Durastic silicone tubing DT08, Allied
Biomedical, Paso Robles, CA) was positioned in the left atrium to
monitor the pressure. The lung lymphatic was cannulated according to
the method of Staub et al. (15) using the modification of
Demling and Gunther (6) to prevent systemic contamination
of the lung lymph. A fifth-interspace right thoracotomy was performed,
and an efferent lymphatic from the caudal mediastinal lymph node was
cannulated (Silastic medical grade tubing 0.025 in. ID, 0.047 in. OD;
Dow Corning, Midland, MI) by a modification of the technique of Staub
et al. The systemic contribution to the caudal mediastinal
lymph node was ligated, and the systemic diaphragmatic lymph vessels
were cauterized through a ninth-interspace thoracotomy incision. The
incision sites were infiltrated with 2% lidocaine to minimize
postoperative pain, and the wounds were closed. During the
postoperative period, buprenex (0.3 mg iv) was administered as needed
for pain. The animals were given 5-7 days to recover from the
surgical procedure, during which time they had free access to food and water.
Burn and smoke inhalation injury.
Before the injury, a tracheostomy was performed under ketamine
anesthesia (Ketaset, Fort Dodge Animal Health, Fort Dodge, IA), and a
cuffed tracheostomy tube (10 mm diameter; Shiley, Irvine, CA) was
inserted. The anesthesia was continued with halothane. Twelve animals
then received a combined injury with a 40% total body surface area
(TBSA) third-degree burn and 48 breaths of cotton smoke inhalation. The
technique has been described in more detail elsewhere
(13). Briefly, after the wool was shaved from the animals,
a Bunsen burner was used to make a 20% TBSA third-degree flame burn on
the left side of the flank. Third-degree burn is not associated with
pain, because nerves in the burned tissue are destroyed. Thereafter,
inhalation injury was induced with a modified bee smoker, as previously
described (9). The bee smoker was filled with 40 g of
burning cotton toweling attached to the tracheostomy tube via a
modified endotracheal tube containing an indwelling thermistor from a
Swan Ganz catheter. Four sets of 12 breaths of smoke (total 48) were
delivered, and the carboxyhemoglobin level was determined immediately
after smoke inhalation. The bee smoker does not require recharging
between sets, inasmuch as the amount of toweling (40 g) is adequate for
the total 48 breaths. The temperature of the smoke was not allowed to
exceed 40°C during the procedure. After smoke insufflations, another
20% TBSA third-degree burn was made on the right flank.
Hemodynamic and oxygenation variables.
Vascular pressures were measured using transducers (model PX-1800,
Baxter, Edwards Critical-Care Division) that were adapted with a
continuous flushing device. The transducers were connected to a
hemodynamic monitor (model 78304A, Hewlett-Packard, Santa Clara, CA).
All hemodynamic measurements were made with the animals awake and in
the standing position. Zero calibrations were taken at the level of the
olecranon joints on the front leg of the animals. Cardiac output was
measured by the thermodilution technique using a cardiac output
computer (model COM-1, Baxter, Edward Critical-Care Division). A 5%
dextrose solution was used as the indicator. Cardiac index was
calculated using standard equations. Blood gases and acid-base balance
were measured using a blood gas analyzer (model IL 1600, Instrumentation Laboratory, Lexington, MA). Arterial and mixed venous
blood gas results were corrected for the body temperature of the sheep.
Oxyhemoglobin saturation and carboxyhemoglobin concentration were
analyzed with a CO-oximeter (model IL 482, Instrumentation Laboratory).
Lymph and plasma measurements.
The protein composition of lung lymph collected from the major lung
efferent lymphatic is considered to be representative of the free
interstitial edema fluid (17). Lung lymph flow
(
L,lymph) was measured with a graduated test tube
and stopwatch. Lymph and blood samples were collected in EDTA tubes,
and then the colloid osmotic pressure in plasma (
p) and
lung lymph (
i,L) were determined through a semipermeable
membrane in a colloid osmometer (model 4100, Wescor, Logan, UT). Lung
permeability index (PIL) was calculated according to the
following equation
Levels of NO
/NO
(NOx), intermediate and end products of NO
oxidation, in plasma and lymph were measured by a chemiluminescence assay using an NO analyzer (model 745, Antek, Houston, TX).
Study groups.
Animals were randomized into three groups. The control group received
no injury and no treatment (n = 6). The nontreatment group sustained thermal burn and inhalation smoke injury but was not
treated with LAM-(1-3) (n = 6). The
LAM-(1-3) group received LAM-(1-3)
(1 mg/kg) 1 h after injury (n = 6). Saturating
concentrations of LAM-(1-3) throughout the
experiments were ensured by flow cytometric measurements of neutrophil
surface L-selectin in the absence and presence of excess exogenous
LAM-(1-3). In every instance, no increase in staining
was noted by the addition of exogenous LAM-(1-3), indicating that saturating concentrations of
LAM-(1-3) were present.
Experimental protocol.
Twenty-four hours before the experiment, vascular catheters were
connected to the monitoring devices and maintenance fluid administration (Ringer lactate, 2 ml/kg) via the femoral vein was
started. After baseline measurements (0 h) and sample collections were
completed, the nontreatment and LAM-(1-3) groups
received burn and smoke inhalation injury (see above). The control
group underwent the same procedure, including the tracheostomy and
anesthesia, but did not receive any injury. A silicone Foley catheter
(Dover, 14-Fr, 5 ml; Sherwood Medical, St. Louis, MO) was placed in the urinary bladder for determination of urine output. Immediately after
injury, anesthesia was discontinued and the animals were allowed to
awaken but were maintained on mechanical ventilation (Servo Ventilator
900C, Seimens-Elema) throughout the 48-h experimental period.
Ventilation was performed with a positive end-expiratory pressure of 5 cmH2O and a tidal volume of 15 mg/kg. During the first
3 h after injury, the inspiratory O2 concentration was
maintained at 100% and respiratory rate was kept at 30/min to induce
rapid clearance of carboxyhemoglobin after the smoke inhalation. The control animals were mechanically ventilated in the same fashion. Then
ventilation was adjusted according to blood gas analyses to maintain
the arterial O2 saturation above 90% and the
PCO2 between 25 and 30 mmHg. Fluid
resuscitation during the experiment was performed with Ringer lactate
solution following the Parkland formula (4 ml per percent burned
surface area per kilogram for the first 24 h and 2 ml per percent
burned surface area per kilogram for the next 24 h). One-half of
the volume for the 1st day was infused in the initial 8 h, and the
remainder was infused in the next 16 h (5). Fluid
balance was determined by urine output every 3 h subtracted from
total fluid volume infused. Net fluid balance accumulation was
calculated and represented as milliliters per kilogram per hour. During
this experiment, the animals were allowed free access to food, but not
water, to accurately measure fluid intake.
The lymph and blood samples for determination of total protein
concentration, colloid osmotic pressure, and NOx
were collected at 3, 6, 12, 18, 24, 36, and 48 h after injury in
all three groups. Hemodynamic variables and blood gases were obtained at 3, 6, 12, 18, 24, 30, 36, 42, and 48 h after injury in all groups.
Death and necropsy.
Forty-eight hours after injury, all animals were anesthetized with 500 mg of ketamine and killed with a 60-ml bolus of a saturated KCl
solution injected into the left atrial catheter. Once death was
confirmed by absence of pulse and blood pressure, necropsy was
performed. Lung tissue was obtained for histopathological examination
following a standardized sampling protocol. A 1-cm slice through the
lower lobe of the right lung was injected with 10% buffered formalin
and then immersed in fixative for 3-5 days. After fixation, the
tissue slice was sampled by a technician unaware of the sample status.
Sampling consisted of excising three areas of the lung slice and
placing the tissue in processing cassettes. After the tissue was
sampled, it was embedded in Paraplast, sectioned at 4 µm, and stained
with hematoxylin and eosin. All slides were then masked for assessments
of parenchyma histopathology and airway obstruction following
standardized procedures. Histopathology assessment consisted of
assigning a semiquantitative score for degrees of congestion, edema,
inflammation, and hemorrhage for 24 individual fields under a ×10
objective from the three slides from each animal. Semiquantitative
scores were 0 (appears normal), 1 (light), 2 (moderate), 3 (strong),
and 4 (intense). After completion of the 24 individual assessments for
each category, a mean category score was determined for each animal.
After assessment of parenchymal histopathology, airway obstruction was
evaluated with a standardized procedure. All cross-sectioned airways
were identified in each slide and classified on the basis of the score
assigned. Bronchial airways had associated mucus glands and/or
cartilage, bronchiolar airways lacked mucus glands, and cartilage and
terminal/respiratory bronchioles were identified as having short
cubodial lining epithelial cells that lacked surrounding smooth muscle
tissue. For each airway, a degree of luminal obstruction was then
estimated: 0-100% obstruction. From these data, mean degrees of
bronchial, bronchiolar, and terminal/respiratory bronchiolar
obstruction were determined for each animal.
Statistical methods.
Summary statistics of data are expressed as means ± SE. Data were
analyzed using analysis of variance for a two-factor experiment with
repeated measures over time. Fisher's least significant difference procedure was used for multiple comparisons (or post hoc analysis). For
the histological study, a nonparametric Kruskal-Wallis test was
performed, and Mann-Whitney's U-test was used to compare
data within the groups. Measurements at various times were tested at the 0.05 level of significance.
 |
RESULTS |
The arterial carboxyhemoglobin levels immediately after smoke
exposure were 75.4 ± 9.1% in the nontreatment group and
55.9 ± 5.0% in the LAM-(1-3) group. There was
no statistical difference between these values. All animals survived
the 48-h experimental period.
Pulmonary transvascular fluid flux.
The nontreatment group showed a significant increase in the lung lymph
flow (Fig. 1A), whereas in the
LAM-(1-3) group, antibody treatment significantly
attenuated the increased lung lymph flow. Lung permeability index after
the combined injury was significantly attenuated by
LAM-(1-3) (Fig. 1B).

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Fig. 1.
Pulmonary transvascular fluid flux: lung lymph flow
(A) and lung permeability index (B). Values are
means ± SE. , Control group (n = 6); , nontreatment group (n = 6);
, leukocyte adhesion molecule
(LAM)-(1-3) group (n = 6).
*P < 0.05 vs. baseline; P < 0.05 vs. nontreatment group.
|
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Gas exchange and pulmonary hemodynamics.
The nontreatment group showed a progressive fall in the ratio of
arterial PO2 to inspired O2
fraction (PaO2/FIO2
ratio). It fell significantly from the baseline value 12 h after
injury. In the LAM-(1-3) group, it remained above
that of the nontreatment group for a significant portion of the
experimental period (12 h). There was no significant difference in the
PaO2/FIO2 ratio between
the nontreatment group and the LAM-(1-3) group during the remainder of the period of observation (Fig.
2A). Changes in the
intrapulmonary shunt fraction paralleled those in the
PaO2/FIO2 ratio (Fig.
2B).

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Fig. 2.
Gas exchange and pulmonary hemodynamics: arterial
PO2-to-inspired O2 fraction
(PaO2/FIO2) ratio
(A) and intrapulmonary shunt fraction (B). Values
are means ± SE. See Fig. 1 legend for explanation of symbols.
*P < 0.05 vs. baseline; P < 0.05 vs. nontreatment group.
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Plasma and lung lymph NOx and conjugated dienes.
In the control group, NOx amounts in plasma and
lung lymph increased after anesthesia and then gradually returned toward baseline. In contrast, NOx levels
increased significantly in the nontreatment and
LAM-(1-3) groups throughout the experiment. The
NOx amounts for the LAM-(1-3)
group were lower during the latter part of the period of observation
(Fig. 3A).
NOx levels were virtually the same in the lung
lymph of the injured groups (Fig. 3B). Plasma and lymph
conjugated dienes did not increase in the control group. Conjugated
dienes rose to the same extent in the injured animals with or without
treatment (Fig. 4). However, given the
fact that the lung lymph flow was much higher in the nontreatment
group, nontreated sheep produced a much larger amount of
NOx and lipid peroxidation than the
LAM-(1-3)-treated animals.

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Fig. 3.
Nitrate/nitrite (NOx) levels in
plasma (A) and lung lymph (B). Values are
means ± SE. See Fig. 1 legend for explanation of symbols.
*P < 0.05 vs. baseline; P < 0.05 vs. nontreatment group.
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Fig. 4.
Conjugated dienes in plasma (A) and lymph
(B). Values are means ± SE. See Fig. 1 legend for
explanation of symbols. *P < 0.05 vs. baseline;
P < 0.05 vs. nontreatment group.
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|
Cardiopulmonary hemodynamics.
A summary of the cardiopulmonary hemodynamic data is shown in Table
1. The control group did not show any
significant changes in cardiopulmonary hemodynamic data during the
experimental period. At 3 h after the combined injury in the
LAM-(1-3) and nontreatment groups, cardiac index
(cardiac output/body surface area) decreased significantly compared
with baseline and gradually returned toward baseline values (Fig.
5A). Despite the initial
decrease in cardiac index, mean arterial pressure was maintained during
the study in the nontreatment and LAM-(1-3) groups
(Table 1). The pulmonary arterial pressure rose in the injured animals.
However, the increase was less in the group treated with the antibody
to L-selectin before 36 h (Fig. 5B). Pulmonary
capillary wedge pressure increased in all groups. No statistical
differences were found between the groups (Table 1).

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Fig. 5.
A: cardiac index. B: pulmonary
arterial pressure (PAP). Values are means ± SE. See Fig. 1 legend
for explanation of symbols. *P < 0.05 vs. baseline;
P < 0.05 vs. nontreatment group.
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Lung wet-to-dry weight ratio.
Lung wet-to-dry weight (W/D) ratio was assessed to evaluate the water
content of the lung. The W/D ratio significantly increased after the
smoke inhalation and burn in the nontreatment group. On the other hand,
there was no statistical difference between noninjured control and
LAM-(1-3)-treated animals (Fig.
6).

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Fig. 6.
Lung wet-to-dry weight ratio in control, nontreatment,
and LAM-(1-3) groups. Values are means ± SE
(n = 6). *P < 0.05 vs. control.
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Histopathological examination.
Lung histological changes were evaluated by pathologists who were
unaware of the animal grouping. Although blood gas exchange was
decreased significantly in the injured animals (Fig. 4), we could not
detect histological differences in the scores of edema, congestion,
inflammation (leukocyte infiltration), and hemorrhage after injury with
or without treatment (Fig. 7). In
contrast, airway obstruction was significantly elevated in the injured
groups, especially at the level of the bronchioles (Fig.
8). Administration of
LAM-(1-3) tended to reduce the airway obstruction,
but no statistical difference was found.

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Fig. 7.
Histopathological data. Values are means ± SE
(n = 6). Open bars, control group; solid bars,
nontreatment group; hatched bars, LAM-(1-3) group.
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Fig. 8.
Percentage of airway obstructed by cast formation in
bronchi (A) and bronchioles (B). Values are
means ± SE. *P < 0.05 vs. control. ,
individual animal; , mean for group.
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Changes in leukocyte numbers.
Complete blood count was performed by Hemavet (automatic veterinary CBC
analyzer; CDC Technologies, Oxford, CT) at the setting of sheep. Total
white cell count was increased in the LAM-(1-3) and
control groups but was less in the LAM-(1-3) group.
The neutrophil count also increased in the control group but was
significantly less in the LAM-(1-3) group than in the
control group (Fig. 9).

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Fig. 9.
Total white cell (WBC) count (A) and
neutrophil count (B) in blood samples from femoral artery
line. , control; ,
LAM-(1-3) group. *P < 0.05 vs.
control.
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 |
DISCUSSION |
We previously reported that administration of
LAM-(1-3) antibody could reduce the pulmonary
transvascular fluid flux that occurs after the combination burn injury
to skin and smoke (13). In this study,
LAM-(1-3) was again administered as an
F(ab')2 fragment. In contrast to our previous work
(pretreatment study), the antibody was administered 1 h after
injury. Although our previous study indicated a role for L-selectin in
the response, the therapeutic value of anti-L-selectin antibody could
not be ascertained, because the antibody was given before the injury.
However, it is feasible that an injured patient might practically
receive therapy 1 h after injury. Our demonstration that treatment
with LAM-(1-3) 1 h after injury can minimize the
changes in pulmonary transvascular fluid flux, urinary retention, and
pulmonary arterial pressure may be of therapeutic advantage. The
finding that gas exchange was not improved by treatment with the
antibody is similar to the finding in our previous study
(13). These data support the concept that the elevation in
shunt blood flow seen with the injury is the result of a mechanism
independent of L-selectin. A possible mechanism responsible for the
increased pulmonary shunt blood flow is the increase in NO in the lung.
Consistent with this speculation, LAM-(1-3) did not
inhibit the increase in lung lymph NOx levels.
It is of interest that blockade of L-selectin can virtually prevent the
early changes in pulmonary transvascular fluid flux, even though the
antibody was not given until 1 h after insult. This finding is
consistent with our former hypothesis that the airway was the site of
the initial injury. We previously reported that bronchial blood flow
(blood flow to the airway) increases almost immediately
(2). Within 20 min of smoke inhalation, the bronchial
blood flow increases 10- to 15-fold. Magno and Fishman (10) showed that the tracheal bronchial artery is one of
the major sources of blood to the lung. We have also reported that occlusion of the bronchial artery prevented the increase in pulmonary transvascular fluid flux seen with inhalation injury (3,
12). These findings were recently confirmed by others
(7). We originally suggested that the injury to the airway
resulted in an increase in bronchial microvasculature flow and
permeability. The injured airway possibly releases materials into the
bronchial venous drainage that flow to the pulmonary microvasculature
and cause neutrophils to adhere and become activated in the lung. We
would now add to the hypothesis that the substance(s) released into the
bronchial venous drainage leads to interaction of L-selectin with its
counterstructure. We are now planning to investigate the effect of
LAM-(1-3) on bronchial blood flow. Further study is warranted.
It is of considerable interest that LAM-(1-3) reduced
cast formation at the alveolar level. Casting is a result of a plasma exudate, along with mucus secretion and inflammatory cell infiltration (8). We have reported that the airway epithelium is shed,
leaving a naked basement membrane, immediately after smoke inhalation (1). As a result of the loss of the epithelium, an exudate is formed (4, 8). Exudate formation is not seen with
bronchial artery occlusion, and there is no cast formation in these
animals (12). Nor does the
PaO2/FIO2 ratio fall
after burn and smoke inhalation in these animals. Administration of
LAM-(1-3) showed a trend for inhibiting the cast
formation, possibly because casting at this level contains many
neutrophils, and L-selectin is important for neutrophil infiltration
into the airway. However, the trend was not statistically different.
According to the power analysis, we need 7-20 more animals in each
group to find differences in an airway obstruction study. Taken
together, these findings suggest that obstruction at the bronchiolar
level may not be strongly correlated with decreased gas exchange. They
also suggest that neutrophil emigration into the airway is not
necessary for compromise of gas exchange.
During the latter part of the period of observation, the lung lymph
flow rose in the group given the antibody to L-selectin. We obtained
plasma samples from several animals and ensured that neutralizing
antibody remained throughout the experimental period. However, given
the large number of occluded airways, it is possible that
volutrauma/barotrauma is occurring in these animals because of the 15 ml/kg tidal volume. Stretch can cause the release of cytokines, which
can lead to further damage to the alveoli (16).
Because we were blocking the interaction of neutrophils with
endothelial cells, we tested the complete blood count during the study.
As we showed in Fig. 9, the neutrophil number in the peripheral blood
was significantly less in the LAM-(1-3) group. We
expected that if the cell adhesion were inhibited by blocking L-selectin, peripheral neutrophil number would be higher, although the
result was opposite. We cannot tell the exact reason for this finding.
Probably the inhibition of interaction between neutrophils and
endothelial cells might inhibit the cell activation, and, consequently,
leukocyte induction from the bone marrow would be less.
In conclusion, the posttreatment with the antibody for L-selectin
decreased the lung lymph flow and pulmonary permeability (W/D ratio).
L-selectin appears to be principally involved in the increased
pulmonary transvascular fluid flux observed with burn/smoke insult.
L-selectin may be a useful target in the treatment of acute lung injury
after burn and smoke inhalation.
This work was supported by Shriners of North America Grants 8450, 8610, and 8680 and National Institute of General Medical Sciences Grant
GM-60688.
Address for reprint requests and other correspondence: D. L. Traber, Dept. of Anesthesiology, University of Texas Medical Branch,
301 University Blvd., Galveston, TX 77555-0591 (E-mail: dltraber{at}utmb.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.