THE ROLE OF PLATELET-ACTIVATING-FACTOR AND PEPTIDOLEUKOTRIENES IN THE VASCULAR CHANGES OF RAT PASSIVE ANAPHYLAXIS

被引:15
作者
FERNANDEZGALLARDO, S
GIJON, MA
GARCIA, C
FURIO, V
LIU, FT
CRESPO, MS
机构
[1] CSIC, FDN JIMENEZ DIAZ, AV REYES CATOLICOS 2, E-28040 MADRID, SPAIN
[2] HOSP UNIV SAN CARLOS, SECC MICROSCOPIA ELECTR, E-28040 MADRID, SPAIN
[3] MED BIOL INST, LA JOLLA, CA 92037 USA
关键词
ANAPHYLAXIS; HYPERSENSITIVITY; IGE; INFLAMMATORY MEDIATOR; LEUKOTRIENES; PAF; PAF ANTAGONISTS; SHOCK;
D O I
10.1111/j.1476-5381.1992.tb14221.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The role of platelet-activating factor (PAF) and peptidoleukotrienes as putative mediators of some of the vascular changes triggered by antigen was investigated in rats passively sensitized with monoclonal anti-DNP (2,4-dinitrophenyl) IgE. 2 Lethal anaphylaxis with respiratory distress, systemic hypotension, detachment of the intestinal mucosa, leukopenia and extravasation of protein-rich plasma was observed after antigen challenge of rats sensitized with partially purified monoclonal IgE at concentrations of 15 mg protein kg-1. 3 Analysis of the peritoneal fluid obtained after i.v. challenge with DNP-BSA (bovine serum albumin) showed the presence of significant amounts of PAF (101 +/- 8 pg/rat), whereas this mediator was undetectable in control animals. Leukotriene D4 was the predominant peptidoleukotriene that could be recovered after antigen challenge, and showed an extremely high concentration (92 +/- 15 ng/rat) as compared to PAF levels. 4 Extravasation of protein-rich plasma was observed shortly after challenge and reached a maximum at 30 min. Treatment of animals with i.v. PCA 4248 (1-2 mg kg-1) and WEB 2086 (1 mg kg-1), two chemically unrelated compounds which are antagonists of the PAF-receptor, produced a significant reduction of the extravasation of protein-rich plasma. 5 The same degree of protection could be afforded by MK-886, an inhibitor of leukotriene biosynthesis. Combined treatment with WEB 2086 and MK-886 provided greater inhibition of protein-rich plasma extravasation than either compound alone. PCA 4248 was also found to inhibit in a dose-dependent manner the systemic hypotension observed upon DNP-BSA challenge. 6 These data indicate that the lipid mediators PAF and peptidoleukotrienes are major effectors of the vascular disturbances observed in rat passive IgE-mediated anaphylaxis.
引用
收藏
页码:119 / 125
页数:7
相关论文
共 56 条
[1]  
BENVENISTE J, 1979, CR ACAD SCI D NAT, V289, P1037
[2]   STRUCTURAL-ANALYSIS OF PURIFIED PLATELET-ACTIVATING FACTOR BY LIPASES [J].
BENVENISTE, J ;
LECOUEDIC, JP ;
POLONSKY, J ;
TENCE, M .
NATURE, 1977, 269 (5624) :170-171
[3]   ANTIHYPERTENSIVE ACTIVITY OF AN ALKYL ETHER ANALOG OF PHOSPHATIDYLCHOLINE [J].
BLANK, ML ;
SNYDER, F ;
BYERS, LW ;
BROOKS, B ;
MUIRHEAD, EE .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1979, 90 (04) :1194-1200
[4]   IMPROVED HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC METHOD FOR ISOLATION OF PLATELET-ACTIVATING FACTOR FROM OTHER PHOSPHOLIPIDS [J].
BLANK, ML ;
SNYDER, F .
JOURNAL OF CHROMATOGRAPHY, 1983, 273 (02) :415-420
[5]  
BLIGH EG, 1959, CAN J BIOCHEM PHYS, V37, P911
[6]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[7]   INTERACTION BETWEEN IGE COMPLEXES AND MACROPHAGES IN RAT - NEW MECHANISM OF MACROPHAGE ACTIVATION [J].
CAPRON, A ;
DESSAINT, JP ;
JOSEPH, M ;
ROUSSEAUX, R ;
CAPRON, M ;
BAZIN, H .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1977, 7 (05) :315-322
[8]   PRESENCE OF PLATELET-ACTIVATING FACTOR IN BLOOD FROM HUMANS AND EXPERIMENTAL-ANIMALS - ITS ABSENCE IN ANEPHRIC INDIVIDUALS [J].
CARAMELO, C ;
FERNANDEZGALLARDO, S ;
MARINCAO, D ;
INARREA, P ;
SANTOS, JC ;
LOPEZNOVOA, JM ;
CRESPO, MS .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1984, 120 (03) :789-796
[9]  
CASALSSTENZEL J, 1987, J PHARMACOL EXP THER, V241, P974
[10]   PLATELET-ACTIVATING-FACTOR MEDIATES HEMODYNAMIC-CHANGES AND LUNG INJURY IN ENDOTOXIN-TREATED RATS [J].
CHANG, SW ;
FEDDERSEN, CO ;
HENSON, PM ;
VOELKEL, NF .
JOURNAL OF CLINICAL INVESTIGATION, 1987, 79 (05) :1498-1509