Differential sensitivity of mouse strains to platelet activating factor-induced vasopermeability and mortality: effect of antagonists.

Abstract

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.