CD11B CD18 INTEGRIN AND A BETA-GLUCAN RECEPTOR ACT IN CONCERT TO INDUCE THE SYNTHESIS OF PLATELET-ACTIVATING-FACTOR BY MONOCYTES/

We determined the mechanism by which opsonized zymosan particles, whic h are derived from yeast and composed of carbohydrate polymers, stimul ate platelet-activating factor (PAF) synthesis by monocytes. A role fo r CD11b/CD18 was demonstrated because antibodies to this integrin decr eased PAF synthesis, zymosan bearing only a ligand for CD11b/CD18 (iC3 b) induced the synthesis of PAF, and monocytes that did not express CD 11b/CD18 produced much less PAF than control monocytes. Ligation of CD 11b/CD18 was not sufficient for PAF synthesis suggesting that an addit ional receptor was involved. Monocytes are known to bind beta-glucan w hich is a major component of zymosan. Opsonized beta-glucan particles stimulated the synthesis of PAF, and a soluble form of beta-glucan par tially inhibited PAF synthesis in response to opsonized zymosan. Two l ines of evidence suggested that the beta-glucan receptor mediating thi s response was distinct from CD11b/CD18. First, CD11b/CD18-deficient m onocytes produced PAF when stimulated by zymosan opsonized with isolat ed C3b, a molecule that binds to complement receptor type 1 (CD35). Se cond, inducing contact of monocytes with zymosan by centrifugation res ulted in PAF synthesis that was not inhibited by antibodies to CD11b/C D18. The combination of soluble beta-glucan and antibodies to CD11b/CD 18 completely blocked PAF synthesis in response to opsonized zymosan. Together, these results demonstrate that induction of maximal PAF synt hesis by serum-opsonized zymosan requires the concerted interactions o f monocyte receptors for iC3b and beta-glucan. Additionally, they sugg est that CD11b/CD18 facilitates binding of the particle and that a bet a-glucan receptor transduces the activation signal.