Differential sensitivity of mouse strains to platelet activating factor-induced vasopermeability and mortality: effect of antagonists.
In the present study, we have compared the responses to platelet-activating factor (PAF) of A/J and BALB/c inbred mouse strains. Two PAF-induced events were analyzed: increased vasopermeability, measured by extravasation of Evans blue dye (EB), and mortality. PAF injected into the peritoneal cavity induced a bell-shaped dose-response curve of EB extravasation in both strains of mouse. In A/J mice, maximal EB extravasation was reached with 0.1 microgram of PAF/mouse, whereas in BALB/c mice maximal extravasation was attained at a 10-fold greater PAF concentration. PAF-induced mortality also differed among these mouse strains; the LD50 was 12.1 micrograms/kg in A/J and 21.2 micrograms/kg in BALB/c mice. Thus, these strains differ significantly regarding both events mediated by PAF. Surprisingly, the F1 hybrid (A/J x BALB/c) mice were as sensitive as the A/J strain to PAF-induced extravasation but were as resistant as the BALB/c mice to PAF-induced mortality. The effects of the PAF antagonists BN 52021 and WEB 2086 were compared in the F1 hybrids. It was found that 1.0 mg/kg of WEB 2086 affected PAF-induced extravasation at almost all PAF doses tested (0.03-3.0 micrograms) while 15 mg/kg of BN 52021 was only effective at doses of PAF below 0.3 microgram. Both antagonists prevented PAF-induced mortality. Our results indicate that the two events induced by PAF may be controlled by different genes.
Vásquez-Bravo
Y L
YL
Department of Immunology, University of São Paulo, Brazil.
Russo
M
M
Jancar
S
S
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002199:Capillary Permeability; D004396:Coloring Agents; D004224:Diterpenes; D005070:Evans Blue; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology* / Q000633:toxicity; D013045:Species Specificity; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D004396:Coloring Agents; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086; D005070:Evans Blue; C045856:ginkgolide B