Ability of teicoplanin and vancomycin to induce contraction of, and histamine release from, pulmonary tissue of humans, monkeys and guinea pigs

Takeshi Nabea, Hideki Yamamuraa, Masakazu Hatanakaa, Naoki Shinodaa, Kaname Shimizua, Nobuaki Mizutania, Kazunori Yamashitaa, Michiaki Horibab and Shigekatsu Kohnoa,*

a Department of Pharmacology, Kyoto Pharmaceutical University, 5 Misasagi-Nakauchi, Yamashina, Kyoto 607-8414; b Department of Pneumology, Ogaki Municipal Hospital, 4-86 Minaminokawa-cho, Ogaki, Gifu 503-8502, Japan


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
To assess the safety of teicoplanin and vancomycin with respect to airway tissue, we evaluated whether these two antibiotics induce pulmonary tissue contraction and histamine release in human, monkey and guinea pig specimens in vitro. The effects of these drugs on the release of histamine from monkey blood leucocytes and mouse bone marrow-derived mast cells (BMMC) were also studied. Neither teicoplanin nor vancomycin (10-6 – 10-3 g/mL) induced contractions of guinea pig trachea or lung parenchyma. Similarly, these drugs induced no appreciable change in the resting tonus of cynomolgus monkey bronchus or lung parenchyma. The tonus of monkey trachea was not influenced by teicoplanin, whereas 10-3 g/mL vancomycin caused contraction. The spontaneous tonus of human lung parenchyma was not altered by teicoplanin or vancomycin, and that of the bronchus was not influenced by teicoplanin; however, 10-3 g/mL vancomycin elicited obvious contraction of the bronchus. Neither drug promoted the release of significant amounts of histamine from these pulmonary tissues or from monkey blood leucocytes and BMMC. These results suggest that, compared with vancomycin, teicoplanin may be associated with a lower risk of inducing bronchospasm when used for inhalation therapy.


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Teicoplanin is a glycopeptide antibiotic, similar to vancomycin in terms of structure and activity. It is effective against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA). 1 ,2 ,3 ,4 Intravenous administration of vancomycin has been associated with `red man syndrome'. 5 ,6 ,7 ,8 ,9 ,10 ,11 ,12 ,13 This adverse reaction is characterized by erythema, pruritus and, in severe cases, hypotension and cardiovascular complications. Reaction severity has been correlated with the elevation of histamine concentration in peripheral blood by some researchers. 12 ,13 However, other studies have reported that intravenous infusion of teicoplanin was not associated with such side effects. 14

Aerosolized antibiotics are effective against organisms causing persistent respiratory tract infections in patients with chronic pulmonary diseases. 15 Weathers et al. 16 reported that aerosolized vancomycin effectively eradicated MRSA colonization of the airways. However, aerosolized antibiotics can cause bronchospasm. 17 ,18 Therefore, Weathers et al. 16 gave vancomycin mist in combination with a nebulized ß-agonistic bronchodilator (albuterol). It is therefore very important to evaluate experimentally the effects of teicoplanin and vancomycin on airway tissue at the time of inhalation therapy trials of these drugs.

In the present study, we evaluated whether teicoplanin and vancomycin induce pulmonary tissue contraction and histamine release in pulmonary tissue specimens obtained from several species including humans, and compared these responses with anaphylactic reactions. We also studied the ability of these antibiotics to promote histamine release from monkey blood leucocytes and mouse bone marrow-derived mast cells (BMMC).


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Drugs

Teicoplanin (Hoechst Marion Roussel, Frankfurt, Germany) and vancomycin hydrochloride (Sigma Chemical Co., St Louis, MO, USA) were used. Teicoplanin was dissolved in and diluted with distilled water. Vancomycin was suspended in distilled water at 1.6 x 10-1 g/mL and dissolved by adding 1 N NaOH to the suspension, followed by dilution with distilled water to the required concentration. These preparations were prepared just before use, under shielding from light.

Animals

Male Hartley guinea pigs weighing 800–950 g, 8-week-old male BALB/c mice weighing 22–27 g, and male and female cynomolgus monkeys (Macaca irus) weighing 2.8–4.4 kg (Japan SLC, Hamamatsu, Japan) were used. The animals were used after being held in stock for 3–6 weeks in an air-conditioned room at a temperature of 22 ± 1.5°C and a relative humidity of 55 ± 15%. Artificial illumination was provided from 8.00 a.m. to 8.00 p.m. The animals were fed a standard laboratory diet and given water ad libitum.

The study protocol was approved by the Experimental Animal Research Committee of Kyoto Pharmaceutical University.

Human lung

Macroscopically normal portions of human lungs, which were obtained from patients undergoing resection for carcinoma, were used in experiments as soon as possible. Informed consent was obtained from all patients.

Antigens

Benzylpenicilloyl bovine {gamma}-globulin (BPO-BGG) was prepared according to the method of Levine & Redmond. 19 Mite extracts (from Dermatofagoides farinae) were kindly donated by Dr H. Nagai of Gifu Pharmaceutical University (Gifu, Japan). Dinitrophenylated Ascaris suum extracts (DNP-As) were prepared according to the method of Tada & Okumura. 20

Antisera

Anti-BPO-BGG guinea pig serum was obtained by immunizing 5-week-old female guinea pigs (Japan SLC, Hamamatsu, Japan) with BPO-BGG containing Al(OH)3 as an adjuvant according to the method of Levine et al. 21 (7 day passive cutaneous anaphylaxis (PCA) titre: 1:2500). For antisera against mite extracts, mite-sensitive human atopic serum with a radioallergosorbent test value of >30% was used. Anti-DNP-As rat serum was prepared by immunizing 8-week-old male Brown Norway rats (Seac Yoshitomi, Fukuoka, Japan) with DNP-As containing Bordetella pertussis adjuvant (Kaken Pharmaceutical Co., Tokyo, Japan) according to the method of Tada & Okumura 20 (48 h PCA titre: 1:3500).

Preparation of isolated pulmonary tissues

Guinea pigs. Guinea pigs were passively sensitized by iv injection of anti-BPO-BGG guinea pig serum (1 mL/ animal). Two days later, the animals were killed by exsanguination under pentobarbital (Nembutal, Abbott Laboratories, North Chicago, IL, USA, 40 mg/kg, ip) anaesthesia, and the lung was perfused via a pulmonary artery with Ca2+-free Tyrode's solution (20 mL/animal). The lung and trachea were removed, and tissue strips were prepared as described previously. 22 ,23 In brief, the procedures were as follows. The isolated trachea was split longitudinally through the ventral cartilage; segments (two cartilage rings in width) were cut, and ligatures were tied to the cartilage end. The isolated tracheal preparation consisted of three segments. Lung parenchymal strips consisted of a piece of the lung surface cut into a cylindrical strip.

Monkey. Animals were killed by exsanguination from the cervical artery under ketamine hydrochloride (Sigma Chemical Co., 13 mg/kg, ip) and pentobarbital (10–20 mg/kg, ip) anaesthesia. The lung was then perfused via a pulmonary artery with Ca2+-free Tyrode's solution (50 mL/animal). The lung and trachea were removed, and strips of trachea, bronchus, and lung parenchyma were prepared as follows. The isolated trachea was split longitudinally through the ventral cartilage; segments (one cartilage ring in width) were cut, and the isolated tracheal preparation consisted of one segment. Bronchial strips, 1.5 mm in width and 2 cm in length, were prepared by cutting the primary bronchus spirally. After removing the pleura, cylindrical lung strips, 3 mm in diameter and 2 cm in length, were prepared from the peripheral lung. These preparations were passively sensitized with a ten-fold dilution of human atopic serum (1 mL/preparation for trachea and bronchi, and 2 mL/preparation for lung parenchyma) for 1.5 h at 37°C. After completion of sensitization, the preparation was washed with Ca2+-free Tyrode's solution before suspension in a Magnus bath.

Humans. Bronchial and lung parenchymal strips were prepared as described elsewhere. 22 ,23 Bronchial spiral strips, 1.5 mm in width and 2 cm in length, were prepared. Lung cylindrical strips were prepared as described for the monkey. These preparations were passively sensitized with human atopic serum as described above.

Measurement of movement of isolated pulmonary tissue preparation

The isolated airway tissue preparations were suspended in a 5 mL Magnus bath. The temperature was 37 ± 0.1°C and the loading weight 300 mg. Movement of the smooth muscle was recorded isotonically using a TD-112S isotonic transducer and RGJ 4124 recorder (Nihon Kohden, Tokyo, Japan) through amplification (AA-601H amplifier and EG-650H isotonic coupler; Nihon Kohden). Before beginning the experiments, 5 x10-6 M acetylcholine chloride (Ovisot; Daiichi Pharmaceutical Co., Tokyo, Japan) was repeatedly applied to the isolated preparations until almost equal contractions were observed, indicating that the sensitivity had stabilized. In preparations from guinea pigs and humans, 10-5 M histamine dihydrochloride (Wako Pure Chemical Industries, Osaka, Japan) was then also applied, and the induced contraction was recorded.

Effects of teicoplanin and vancomycin on the resting tonus of the trachea, the bronchus, or lung parenchyma were assessed as follows: Teicoplanin or vancomycin, both at 10-6 10-3 g/mL, was applied cumulatively at 10 min intervals. After drug application, preparations were washed with Tyrode's solution and antigen corresponding to the respective species was added to give a final concentration of 10-5 g/mL; induced contractions were monitored for 10 min. After antigen challenge, KCl was applied ( 10-2 g/mL) to determine maximum contractions.

Reaction solutions in the bath were collected just before and after the cumulative application of teicoplanin or vancomycin and antigen application. The collected medium was then centrifuged (4°C, 15,000g, 2 min) and the resulting supernatant was stored at -20°C until measurement of histamine concentration.

Preparation of lung fragments

Guinea pig. Conditions for passive sensitization of the guinea pig and preparation of lung fragments are described elsewhere. 24 In brief, the isolated lung, obtained from guinea pigs passively sensitized as described above, was cut into pieces measuring 0.25 x 0.25 x 0.25 mm. After washing the lung fragments with Ca2+-free Tyrode's solution, Tyrode's solution (1 mL/100 mg wet tissue) was added to the fragments.

Monkey. As reported previously, 24 the isolated lung was cut into pieces measuring 0.7 x 0.7 x 1–2 mm and washed with Ca2+-free Tyrode's solution. The fragments were passively sensitized by incubation with five-fold diluted human atopic serum for 1.5 h at 37°C. After completion of sensitization, the fragments was washed with Ca2+-free Tyrode's solution and suspended in Tyrode's solution (100 mg wet tissue/mL).

Human. Conditions for preparation of human lung fragments and passive sensitization were similar to those described above and previously for monkeys. 24 ,25

Differentiation and culture of BMMC

BMMC were obtained as described elsewhere. 26 ,27 In brief, bone marrow cells from BALB/c mice were cultured for 5 weeks in {alpha}-medium supplemented with 20% horse serum, 100 µM 2-mercaptoethanol, 100 µM non-essential amino acids, 60 µg/mL kanamycin sulphate and 10% or 20% conditioned medium. After 5 weeks of culture, the BMMC were >95% pure as assessed by Alcian Blue staining. BMMC ( 106 cells/mL) were passively sensitized by adding 0.1 volume of anti-DNP-As rat serum to the cell suspension, which was then incubated at 37°C for 24 h. After completion of sensitization, the BMMC were washed and suspended in Tyrode's solution containing 0.1% bovine serum albumin (BSA) to give a cell concentration of 4 x 105 cells/mL.

Preparation of monkey peripheral blood leucocyte suspension

Peripheral blood was drawn in the presence of heparin sodium (Takeda Chemical Industries, Osaka, Japan) from the cervical artery of monkeys under ketamine and pentobarbital anaesthesia. Ten millilitres of the blood was added to 1.75 mL of 6% dextran (Nacalai Tesque, Kyoto, Japan); the mixture was allowed to stand at room temperature for 2 h and the leucocyte layer was collected. After washing with Ca2+-free Tyrode's solution, the obtained leucocytes were passively sensitized by incubation with human atopic serum at 37°C for 1 h. Then, the leucocytes were washed with Ca2+-free Tyrode's solution and suspended at 2 x 107 cells/mL in Tyrode's solution containing 0.1% BSA.

Histamine release from lung fragments or cells

The suspension of lung fragments or cells was preincubated at 37°C for 10 min, then 10-6 – 10-3 g/mL of teicoplanin or vancomycin, or the appropriate antigen (final concentration 10-5 g/mL, except for BMMC (10-7 g/mL)) was added to the suspension followed by 30 min incubation at 37°C. The reaction was terminated by filtration of the fragments on gauze or by cooling the cell suspension. The reacted solution was centrifuged (4°C, 1700g, 10 min), and the resulting supernatant was stored at -20°C until assay of histamine.

Histamine assay

Histamine in the supernatant was assayed fluorimetrically by HPLC over a cation exchange column (TSK gel SP-2SW, 4.6x 50 mm, Tosoh, Tokyo, Japan) as described by Itoh et al., 28 who modified the method of Yamatodani et al. 29 To estimate the histamine contents of tissues or cells that had not been treated with drug or antigen, specimens were placed in a boiling water bath for 10 min after addition of perchloric acid at the final concentration of 3%. After centrifugation at 15,000g for 2 min at 4°C, histamine in the supernatant was measured as described above.

Statistical analyses

Statistical analysis was performed by one-way analysis of variance. If a significant difference was detected, the individual group difference was determined by Bonferroni's multiple test. A P value of <0.05 was considered to indicate statistical significance.


    Results
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Contractions of isolated trachea, bronchus and lung parenchyma, and histamine release from these tissues

Guinea pig trachea and lung parenchyma. As shown in Figure 1 and Table I, neither teicoplanin nor vancomycin induced contraction of, or histamine release from, guinea pig trachea or lung parenchyma. In contrast, antigen provoked both contraction of, and histamine release from, both preparations.



View larger version (14K):
[in this window]
[in a new window]
 
Figure 1. Influence of teicoplanin ({circ}), vancomycin ({blacksquare}) and antigen ({blacktriangleup}) on resting tonus of passively sensitized isolated guinea pig tracheal (a) and lung parenchymal (b) strips. Each point represents the mean ± S.E. of six experiments.

 

View this table:
[in this window]
[in a new window]
 
Table I. Amounts of histamine released from isolated guinea pig tracheal and lung parenchymal strips before and after treatment with teicoplanin, vancomycin or antigen (benzylpenicilloyl bovine {Upsilon}-globulin) in a Magnus bath
 
Monkey trachea, bronchus and lung parenchyma. Antigen elicited contraction of monkey bronchus and lung parenchyma, but neither teicoplanin nor vancomycin at concentrations of 10-6 10-3 g/mL had an appreciable effect on the resting tonus of these tissues. The tonus of the trachea was not influenced by teicoplanin, whereas 10-3 g/mL vancomycin caused an apparent contraction, the degree of which was about 30% of the anaphylactic response (Figure 2). Vancomycin-induced tracheal contraction was observed in two of six animals. Teicoplanin and vancomycin only slightly induced the release of histamine from these monkey pulmonary tissues (Table II).



View larger version (12K):
[in this window]
[in a new window]
 
Figure 2. Influence of teicoplanin ({circ}), vancomycin ({blacksquare}) and antigen ({blacktriangleup}) on resting tonus of passively sensitized isolated monkey tracheal (a), bronchial (b) and lung parenchymal (c) strips. Each point represents the mean ± S.E.of five or six experiments.

 

View this table:
[in this window]
[in a new window]
 
Table II. Amounts of histamine released from isolated monkey tracheal, bronchial and lung parenchymal strips before and after treatment with teicoplanin, vancomycin or antigen (mite extract) in a Magnus bath
 
Human bronchus and lung parenchyma. As shown in Figure 3, the spontaneous tonus of human lung parenchyma was unaltered by teicoplanin or vancomycin and that of the bronchus was unaltered by teicoplanin, whereas 10-3 g/mL vancomycin elicited obvious contraction of the bronchus. Bronchial tension after addition of 10-3 g/mL vancomycin was significantly higher than that after addition of 10-3 g/mL teicoplanin. Such contractions were seen in specimens obtained from four of ten humans. Figure 4 shows an example of the pattern of contraction induced by vancomycin. Of the four preparations, the one shown here is the one that responded most strongly: the bronchus started to contract approximately 1 min after addition of 10-3 g/mL vancomycin, and the reaction plateaued 10 min after addition. The contraction height at the plateau level was virtually equivalent to the height after application of 10-5 M histamine or 10-5 g/mL mite antigen. Nevertheless, neither antibiotic significantly increased the amount of histamine released in the Magnus bath (Table III). In antigen-challenged preparations, both contractions and increased histamine release were observed (Figure 3 and Table III).



View larger version (16K):
[in this window]
[in a new window]
 
Figure 3. Influence of teicoplanin ({circ}), vancomycin ({blacksquare}) and antigen ({blacktriangleup}) on resting tonus of passively sensitized isolated human bronchial (a) and lung parenchymal (b) strips. Each point represents the mean ± S.E.of ten experiments. *: Significant difference at P< 0.05.

 


View larger version (15K):
[in this window]
[in a new window]
 
Figure 4. Actual contractile patterns of isolated human bronchial strips treated with teicoplanin, vancomycin and mite antigen. W: wash

 

View this table:
[in this window]
[in a new window]
 
Table III. Amounts of histamine released from isolated human bronchial and lung parenchymal strips before and after treatment with teicoplanin, vancomycin or antigen (mite extract) in a Magnus bath
 
Histamine release

Lung fragments. Lung fragments from guinea pigs, monkeys and humans spontaneously released about 1% of their total histamine content. Neither teicoplanin nor vancomycin promoted spontaneous histamine release, whereas anaphylactic stimulation significantly increased such release (Table IV).


View this table:
[in this window]
[in a new window]
 
Table IV. Influence of teicoplanin and vancomycin on spontaneous histamine release from lung fragments of guinea pig, monkey and human
 
BMMC. No concentration of teicoplanin and vancomycin tested increased spontaneous histamine release. However, anaphylactic release was noted (Table V).


View this table:
[in this window]
[in a new window]
 
Table V. Influence of teicoplanin and vancomycin on spontaneous histamine release from mouse bone marrow-derived mast cells (BMMC) amd monkey peripheral blood leucocytes
 
Monkey peripheral blood leucocytes. Neither teicoplanin nor vancomycin increased spontaneous histamine release, which was equivalent to about 13% of the total content. In contrast, leucocytes challenged with the appropriate antigen released large amounts of histamine (Table V).


    Discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Although vancomycin induced considerable contraction of monkey trachea and human bronchus at 10-3 g/mL, which is equivalent to the concentration in airway tissues in patients receiving aerosolized vancomycin therapy, 16 teicoplanin caused no contraction of any pulmonary tissue obtained from several species, including humans.{circ} These differences in activity between teicoplanin and vancomycin suggest that teicoplanin has a lower risk of inducing bronchospasm than vancomycin. Neither teicoplanin nor vancomycin had a significant effect on histamine release from these tissues. Histamine release from BMMC and monkey blood leucocytes was not affected by either antibiotic.

Sahai et al. 14 reported that intravenous infusion of vancomycin to humans is associated with a high frequency of `red man syndrome', the severity of which is positively correlated with the increment in histamine concentration in peripheral blood. The occurrence of vancomycin-induced `red man syndrome' has been reported to be inhibited by treating patients with an H1-receptor antagonist. 30 O'Sullivan et al., 31 however, found no relation between this adverse effect and increased blood histamine concentrations, suggesting that other mediators might participate in the development of ` red man syndrome'. Not only histamine 32 ,33 ,34 but also cholinergic agonists, 33 ,34 cysteinyl leukotrienes, 34 ,35 ,36 thromboxane A2, 37 ,38 prostaglandin D2, 38 prostaglandin F2{alpha}, 38 and endothelins, 39 ,40 cause marked contraction of human bronchi. Monkey trachea is known not to respond to histamine. 41 ,42 These previous results and those of the present study suggest that the vancomycin-induced contractions of human bronchus and monkey trachea might be caused primarily by the release or production of mediators other than histamine. However, we cannot rule out the possibility that vancomycin directly causes contraction of smooth muscle. Further studies are needed to elucidate the mechanism of vancomycin-induced contractions.

Polk et al. 43 attempted to predict the severity of `red man syndrome' after intravenous infusion of vancomycin on the basis of the cutaneous response to intradermally administered vancomycin in healthy adults, but noted no significant correlation between the vancomycin-induced flare and the severity of `red man syndrome'. Consistent with the results of that study, we found that vancomycin did not cause the contraction of monkey bronchus, monkey lung parenchyma or human lung parenchyma. In general, relatively central airway tissue is known to contract more in response to neurotransmitters, such as cholinergic agonists, than in response to chemical mediators, such as histamine and arachidonic acid metabolites; the opposite holds true for relatively peripheral airway tissue. These characteristics of airway tissues considered with the organ-specific action of vancomycin lead us to speculate that vancomycin may potently induce contractions of human trachea, although such tissue was not available for the present study.

Neither teicoplanin nor vancomycin induced histamine release from lung fragments of three species, or from BMMC or monkey blood leucocytes. Results of the lung fragment studies agree with those of the experiments using a Magnus bath. The lack of histamine release from BMMC and monkey leucocytes indicates that the sensitivity of these cells to vancomycin differs substantially from that of unidentified cells that are thought to release histamine after intravenous infusion of vancomycin.

In conclusion, our results suggest that, compared with vancomycin, teicoplanin may be associated with a lower risk of bronchoconstriction when used for inhalation therapy and a lower risk of `red man syndrome' when used for infusion therapy.


    Acknowledgments
 
We thank Hoechst Marion Roussel for supplying teicoplanin.


    Notes
 
* Corresponding author. Tel+81-75-595-4667; Fax: +81-75-595-4764; E-mail: kohno{at}mb.kyoto-phu.ac.jp Back


    References
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
1 . Williams, A. H. & Gruneberg, R. N. (1984). Teicoplanin. Journal of AntimicrobialChemotherapy14 , 441 –5.

2 . Williams, A. H. & Gruneberg, R. N. (1988). Teicoplanin revisited. Journal of Antimicrobial Chemotherapy24 , 397 –401.[Abstract]

3 . Lagast, H., Dodion, P. & Klastersky, J. (1986). Comparison of pharmacokinetics and bactericidal activity of teicoplanin and vancomycin. Journal of Antimicrobial Chemotherapy 18 , 513 –20.[Abstract]

4 . Glupczynski, Y., Lagast, H., Van der Auwera, P., Thys, J. P., Crokaert, F., Yourassowsky, E. et al . (1986). Clinical evaluation of teicoplanin for therapy of severe infections caused by gram-positive bacteria. Antimicrobial Agents and Chemotherapy29 , 52 –7.[ISI][Medline]

5 . Garrelts, J. C. & Peterie, J. D. (1985). Vancomycin and the `red man's syndrome'. New England Journal of Medicine 312 , 245 .[ISI][Medline]

6 . Newfield, P. & Roizen, M. F. (1979). Hazards of rapid administration of vancomycin. Annals of Internal Medicine 91 , 581 .[ISI][Medline]

7 . Odio, C., Mohs, E., Sklar, F. H., Nelson, J. D. & McCracken, G. H. (1984). Adverse reactions to vancomycin used as prophylaxis for CSF shunt procedures. American Journal of Diseases of Children138 , 17 –9.[Abstract]

8 . Dajee, H., Laks, H., Miller, J. & Oren, R. (1984). Profound hypotension from rapid vancomycin administration during cardiac operation. Journal of Thoracic and Cardiovascular Surgery 87 , 145 –6.[Abstract]

9 . Pau, A. K. & Khakoo, R. (1985). `Red-neck syndrome' with slow infusion of vancomycin. New England Journal of Medicine 313 , 756 –7.[ISI][Medline]

10 . Davis, R. L., Smith, A. L. & Koup, J. R. (1986). The `red man's syndrome' and slow infusion of vancomycin. Annals of Internal Medicine104 ,285 –6.

11 . Southorn, P. A., Plevak, D. J., Wright, A. J. & Wilson, W. R. (1986). Adverse effects of vancomycin administered in the perioperative period. Mayo Clinic Proceedings61 ,721 –4.[ISI][Medline]

12 . Polk, R. E., Healy, D. P., Schwartz, L. B., Rock, D. T., Garson, M. L. & Roller, K. (1988). Vancomycin and the red-man syndrome: pharmacodynamics of histamine release. Journal of Infectious Diseases157 , 502 –7.[ISI][Medline]

13 . Healy, D. P., Sahai, J. V., Fuller, S. H. & Polk, R. E. (1990). Vancomycin-induced histamine release and `red man syndrome': comparison of 1- and 2-hour infusions. Antimicrobial Agents and Chemotherapy 34 , 550 –4.[ISI][Medline]

14 . Sahai, J., Healy, D. P., Shelton, M. J., Miller, J. S., Ruberg, S. J. & Polk, R. (1990). Comparison of vancomycin- and teicoplanin-induced histamine release and `red man syndrome'. Antimicrobial Agents and Chemotherapy 34, 765 –9.[ISI][Medline]

15 . Kelly, H. W. & Lovato, C. (1984). Antibiotic use in cystic fibrosis. Drug Intelligence and Clinical Pharmacy18 , 772 –83.

16 . Weathers, L., Riggs, D., Santeiro, M. & Weibley, R. E. (1990). Aerosolized vancomycin for treatment of airway colonization by methicillin-resistant Staphylococcus aureus . Pediatric Infectious Disease Journal 9, 220 –1.[ISI][Medline]

17 . Miller, W. F. (1973). Aerosol therapy in acute and chronic respiratory disease. Archives of Internal Medicine 131, 148 –55.[ISI][Medline]

18 . Wanner, A. & Rao, A. (1980). Clinical indications for and effects of bland, mucolytic and antimicrobial aerosols. American Review of Respiratory Disease 122, 79 –87.[ISI][Medline]

19 . Levine, B. B. & Redmond, A. P. (1968). The nature of the antigen– antibody complexes initiating the specific wheal-and-flare reaction in sensitized man. Journal of Clinical Investigation 47, 556 –67.[ISI][Medline]

20 . Tada, T. & Okumura, K. (1971). Regulation of homocytotropic antibody formation in the rat. I. Feed-back regulation by passively administered antibody. Journal of Immunology 106 , 1002 –11.[ISI][Medline]

21 . Levine, B. B., Chang, H. & Vaz, N. M. (1971). The production of hapten-specific reaginic antibodies in the guinea pig. Journal of Immunology 106, 29 –33.[ISI][Medline]

22 . Watanabe-Kohno, S., Yamamura, H., Nabe, T., Horiba, M. & Ohata, K. (1992). MCI-826 is a potent and selective antagonist of peptide leukotrienes (p-LTs) and has characteristics distinctive from those of FPL 55712. Japanese Journal of Pharmacology 60 , 1 –8.[ISI][Medline]

23 . Watanabe-Kohno, S., Yasui, K., Nabe, T., Yamamura, H., Horiba, M. & Ohata, K. (1992). Significant role of peptide leukotrienes (p-LTs) in the antigen-induced contractions of human and guinea pig lung parenchymas and bronchi or tracheas in vitro . Japanese Journal of Pharmacology 60, 209 –16.[ISI][Medline]

24 . Yamamura, H., Taira, M., Negi, H., Nanbu, F., Kohno, S. W. & Ohata, K. (1988). Effect of AA-861, a selective 5-lipoxygenase inhibitor, on models of allergy in several species. Japanese Journal of Pharmacology 47, 261 –71.[ISI][Medline]

25 . Watanabe-Kohno, S., Shimizu, T., Mizuta, J., Ogino, K., Yamamura, H. & Ohata, K. (1990). Effect of procaterol on the isolated airway smooth muscle and the release of anaphylactic chemical mediators from the isolated lung fragments. Arzneimittel-Forschung 40 ,669 –74.[Medline]

26 . Nakano, T., Sonoda, T., Hayashi, A., Yamatodani, Y., Kanayama, Y., Yamamura, T. et al. (1985). Fate of bone marrow-derived cultured mast cells after intracutaneous, intraperitoneal, and intravenous transfer into genetically mast cell-deficient W/Wv mice. Evidence that cultured mast cells can give rise to both connective tissue type and mucosal mast cells. Journal of Experimental Medicine162 , 1025 –43.[Abstract]

27 . Yamamura, H., Nabe, T., Kohno, S. & Ohata, K. (1994). Endothelin-1 induces release of histamine and leukotriene C4 from bone marrow-derived mast cells. European Journal of Pharmacology257 , 235 –42.[ISI][Medline]

28 . Itoh, Y., Oishi, R., Nishibori, M. & Saeki, K. (1989). Histamine turnover in the rat hypothalamic nuclei estimated from {alpha}-fluoromethylhistidine-induced histamine decrease. Japanese Journal of Pharmacology51 , 581 –4.[ISI][Medline]

29 . Yamatodani, A., Fukuda, H., Wada, H., Iwaeda, T. & Watanabe, T. (1985). High-performance liquid chromatographic determination of plasma and brain histamine without previous purification of biological samples: cation-exchange chromatography coupled with post-column derivatization fluorometry. Journal of Chromatography 344, 115 – 23.[Medline]

30 . Sahai, J., Healy, D. P., Garris, R., Berry, A. & Polk, R. E. (1989). Influence of antihistamine pretreatment on vancomycin-induced red-man syndrome. Journal of Infectious Diseases160 , 876 –81.[ISI][Medline]

31 . O'Sullivan, T. L., Ruffing, M. J., Lamp, K. C., Warbasse, L. H. & Rybak, M. J. (1993). Prospective evaluation of red man syndrome in patients receiving vancomycin. Journal of Infectious Diseases168 , 773 –6.[ISI][Medline]

32 . Ruffin, R. E., Dolovich, M. B., Wolff, R. K. & Newhouse, M. T. (1978). The effects of preferential deposition of histamine in the human airway. American Review of Respiratory Disease 117 , 485 –92.[ISI][Medline]

33 . De Jongste, J., Mons, H., Van Strik, R., Bonta, I. & Kerrebijn, K. (1986). Human small airway smooth muscle responses in vitro ; actions and interactions of methacholine, histamine and leukotriene C4.European Journal of Pharmacology125 ,29 –35.[ISI][Medline]

34 . Muccitelli, R. M., Tucker, S. S., Hay, D. W. P., Torphy, T. J. & Wasserman, M. A. (1987). Is the guinea pig trachea a good in vitro model of human large and central airways? Comparison of leukotriene-, methacholine-, histamine- and antigen-induced contractions. Journal of Pharmacology and Experimental Therapeutics 243, 467 –73.[Abstract]

35 . Dahlén, S.-E., Hedqvist, P., Hammarström, S. & Samuelsson, B. (1980). Leukotrienes are potent constrictors of human bronchi. Nature288 , 484 –6.[ISI][Medline]

36 . Hanna, C. J., Bach, M. K., Pare, P. D. & Schellenberg, R. R. (1981). Slow-reacting substances (leukotrienes) contract human airway and pulmonary vascular smooth muscle in vitro. Nature 290, 343 –4.[ISI][Medline]

37 . McKenniff, M., Rodger, I. W., Norman, P. & Gardiner, P. J. (1988). Characterisation of receptors mediating the contractile effects of prostanoids in guinea-pig and human airways. European Journal of Pharmacology 153, 149 –59.[ISI][Medline]

38 . Coleman, R. A. & Sheldrick, R. L. (1989). Prostanoid-induced contraction of human bronchial smooth muscle is mediated by TP-receptors. British Journal of Pharmacology96 , 688 –92.[Abstract]

39 . Henry, P. J., Rigby, P. J., Self, G. J., Preuss, J. M. & Goldie, R. G. (1990). Relationship between endothelin-1 binding site densities and constrictor activities in human and animal airway smooth muscle. British Journal of Pharmacology 100, 786 –92.[Abstract]

40 . Adner, M., Cardell, L. O., Sjoberg, T., Ottosson, A. & Edvinsson, L. (1996). Contractile endothelin-B (ETB) receptors in human small bronchi. European Respiratory Journal 9 ,351 –5.[Abstract/Free Full Text]

41 . Chand, N., Dhawan, B. N., Srimal, R. C., Rahmani, N. H., Shukla, R. K. & Altura, B. M. (1980). Reactivity of trachea, bronchi, and lung strips to histamine and carbachol in rhesus monkeys. Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology 49, 729 –34.

42 . Nagai, H., Kondo, M., Koda, A., Nakamura, S., Hashimoto, M., Yanagihara, Y. et al. (1992). Responses of isolated Japanese monkey tracheal muscle to allergic mediators .International Archives of Allergy and Immunology 98, 70 –5.[ISI][Medline]

43 . Polk, R. E., Israel, D., Wang, J., Venitz, J., Miller, J. & Stotka, J. (1993). Vancomycin skin tests and prediction of `red man syndrome' in healthy volunteers. Antimicrobial Agents and Chemotherapy 37, 2139 –43.[Abstract]

Received 19 May 1998; returned 13 July 1998; revised 31 July 1998; accepted 17 September 1998





This Article
Abstract
FREE Full Text (PDF)
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Disclaimer
Request Permissions
Google Scholar
Articles by Nabe, T.
Articles by Kohno, S.
PubMed
PubMed Citation
Articles by Nabe, T.
Articles by Kohno, S.