Antigen induces leucopenia in non‐immunised guinea‐pigs injected with platelets from actively sensitized animals

Abstract

Ovalbumin administration to animals injected with 0.5–5 × 106 washed platelets μl−1 from actively sensitized animals induced a marked decrease (maximum of around 50% at 60 min) in the number of circulating leucocytes, whereas platelet counts were unaffected. The intensity of the decrease in leucocyte counts was dependent upon the concentration of the injected platelets. No drop in leucocyte counts was measured upon antigen challenge of guinea‐pigs injected with platelets from non‐sensitized animals. This phenomenon was unaffected by pretreatment of the recipient animals with a platelet‐activating factor (PAF) antagonist WEB 2086 (3 mg kg−1 i.v.) but was markedly reduced (around 50% inhibition) by the anti‐allergic drug nedocromil sodium (100 mg kg−1 i.v.). By contrast, indomethacin (5 mg kg−1 i.v.) caused a significant (P < 0.01) enhancement of the antigen‐induced leucopenia, whereas the mixed cyclooxygenase and lipoxygenase inhibitor, BW 755C (10 mg kg−1 i.v.) suppressed the drop in leucocyte counts evoked by ovalbumin administration. These results indicate that platelets from actively sensitized guinea‐pigs transferred to normal animals still responds to the specific antigen with the activation of circulating leucocytes. This phenomenon appears to be independent of the production of PAF and of cyclo‐oxygenase metabolites. By contrast, the production of the metabolites of the lipoxygenase pathway by platelets could account for the marked leucopenia observed following the immunological stimulation.

The effect of cetirizine on antigen‐dependent leucopenia in the guinea‐pig

“…Previous work has suggested an important role for lipoxygenase products as the platelet-dependent leucopenia was inhibited by the mixed lipoxygenase inhibitor BW755C but not indomethacin (Pretolani et al, 1990). In the present series of experiments however, we failed to support a role for lipoxygenase products in this response, as the selective lioxygenase inhibitor BWA4C (Tateson et al, 1988) was ineffective at a concentration previously demonstrated to inhibit the 'leukotriene-dependent' component of bronchial anaphylaxis in the guinea-pig (Payne et al, 1988).…”

“…However, it is unlikely that inhibition of the cyclooxygenase pathway of arachidonic acid metabolism or inhibition of PAF generation is responsible for the efficacy of cetirizine as it has previously been demonstrated that indomethacin and the selective PAF antagonist, WEB 2086, were ineffective in inhibiting the antigen-dependent leucopenia (Pretolani et al, 1990). Cetirizine has also been reported to inhibit the accumulation of leucocytes in the skin of allergic individuals following antigen challenge in vivo (Fadel et al, 1987;Charlesworth et al, 1988;Michel et al, 1988;Henocq & Rihoux, 1990) and will inhibit both PAF and FMLPinduced chemotaxis of human eosinophils in vitro (De Vos et al, 1989).…”

“…We have previously shown that platelets from actively sensitized guinea-pigs when transferred to nonimmunized animals will induce a marked leukopenia following antigen challenge (Pretolani et al, 1990). A central role for lipoxygenase products was proposed as the platelet-dependent leucopenia was attenuated by the dual lipoxygenase-cyclooxygenase inhibitor BW755C, but not by indomethacin.…”

“…Blood was taken into 1/10th final volume sodium citrate (3.8% w/v) in the presence of 1 fM prostacyclin (PGI2). Washed platelets were prepared as described previously (Pretolani et al, 1990). Briefly, platelet rich plasma (PRP) was prepared by centrifugation at 200g for 15min at 30°C.…”