Activation of protein kinase C βII by the stereo-specific phosphatidylserine receptor is required for phagocytosis of apoptotic thymocytes by resident murine tissue macrophages

We showed previously that protein kinase C (PKC) is required for phagocytosis of apoptotic leukocytes by murine alveolar (AMO) and peritoneal macrophages (PMphi) and that such phagocytosis is markedly lower in AMO compared with PMphi. In this study, we examined the roles of individual PKC isoforms in phagocytosis of apoptotic thymocytes by these two Mphi populations. By immunoblotting, Mphi expressed equivalent PKC eta but lower amounts of other isoforms (alpha, betaI, betaII, delta, epsilon, mu, and zeta), with the greatest difference in betaII expression. A requirement for PKC betaII for phagocytosis was demonstrated collectively by phorbol 12-myristate 13-acetate-induced depletion of PKC beta11, by dose-response to PKC inhibitor Ro-32-0432, and by use of PKC beta11 myristoylated peptide as a blocker. Exposure of PMphi to phosphatidylserine (PS) liposomes specifically induced translocation of PKC beta11 and other isoforms to membranes and cytoskeleton. Both AMO and PMphi expressed functional PS receptor, blockade of which inhibited PKC beta11 translocation. Our results indicate that murine tissue Mphi require PKC beta11 for phagocytosis of apoptotic cells, which differs from the PKC isoform requirement previously described in Mphi phagocytosis of other particles, and imply that a crucial action of the PS receptor in this process is PKC 1311 activation.