The role of platelet-activating factor and peptidoleukotrienes in the vascular changes of rat passive anaphylaxis.
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 +2- 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.
Fernández-Gallardo
S
S
Fundación Jiménez Díaz, Centro Asociado al CSIC, Madrid, Spain.
Gijón
M A
MA
García
C
C
Furio
V
V
Liu
F T
FT
Sánchez Crespo
M
M
D000707:Anaphylaxis / Q000503:physiopathology*; D000818:Animals; D001202:Ascitic Fluid / Q000737:chemistry; D001794:Blood Pressure / Q000187:drug effects*; D001798:Blood Proteins / Q000378:metabolism; D004136:Dinitrobenzenes; D007073:Immunoglobulin E / Q000276:immunology; D015289:Leukotrienes / Q000502:physiology*; D008055:Lipids / Q000502:physiology*; D008297:Male; D010455:Peptides / Q000502:physiology*; D010972:Platelet Activating Factor / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012710:Serum Albumin, Bovine
D001798:Blood Proteins; D004136:Dinitrobenzenes; D015289:Leukotrienes; D008055:Lipids; D010455:Peptides; D010972:Platelet Activating Factor; D012710:Serum Albumin, Bovine; D007073:Immunoglobulin E