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-activ ating factor (PAF) of A/J and BALB/c inbred mouse strains. Two PAF-ind uced events were analyzed: increased vasopermeability, measured by ext ravasation of Evans blue dye (EB), and mortality. PAF injected into th e peritoneal cavity induced a bell-shaped dose-response curve of EB ex travasation in both strains of mouse. In A/J mice, maximal EB extravas ation was reached with 0.1 mu g of PAF/mouse, whereas in BALB/c mice m aximal extravasation was attained at a 10-fold greater PAF concentrati on. PAF-induced mortality also differed among these mouse strains; the LD(50) was 12.1 mu g/kg in A/J and 21.2 mu g/kg in BALB/c mice. Thus, these strains differ significantly regarding both events mediated by PAF. Surprisingly, the F-1 hybrid (A/J x BALB/c) mice were as sensitiv e 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 a ntagonists BN 52021 and WEB 2086 were compared in the F-1 hybrids. It was found that 1.0 mg/kg of WEB 2086 affected PAF-induced extravasatio n at almost all PAF doses tested (0.03-3.0 mu g) while 15 mg/kg of BN 52021 was only effective at doses of PAF below 0.3 mu g. Both antagoni sts prevented PAF-induced mortality. Our results indicate that the two events induced by PAF may be controlled by different genes.