Modulation of alveolar macrophage phagocytosis by leukotrienes is Fc receptor-mediated and protein kinase C-dependent

We have previously established an important role for leukotrienes (LTs) in augmenting rat alveolar macrophage (AM) phagocytosis of Klebsiella pneumoni ae opsonized with complete immune serum (IS), which contains the two well-k nown opsonins, immunoglobulin (lg) G and complement (C). In this report, th e specific opsonin requirements for ii modulation of AM phagocytosis and th e dependence of this response on protein kinase (PK) C activity were invest igated. Phagocytosis of K. pneumoniae opsonized with IS, non-immune serum, or heat-inactivated immune serum and of inert targets (IgG-opsonized fluore scent microspheres or C-opsonized sheep red blood cells) was examined. Inhi bition of endogenous LT synthesis or action attenuated, whereas the additio n of exogenous LTs augmented, phagocytosis only of targets opsonized with I gG. LTs had no effect on phagocytosis of C-opsonized or unopsonized targets . LTs did not affect adherence of IgG-opsonized targets, implying instead a n enhancement of internalization. Macrophage internalization of phagocytic targets has previously been shown to require PKC activity. Pretreatment of AMs with the PKC inhibitors staurosporine or calphostin C, or with phorbol 12-myristate 13-acetate to deplete PKC, completely inhibited the ability of LTB4 and largely inhibited the ability of LTC4 to augment phagocytosis of Igc-opsonized microspheres. These results demonstrate that LT enhancement i s confined to Fc receptor (FcR)-mediated phagocytosis. Moreover, PKC activa tion represents an important mechanism by which LTs promote FcR-mediated ph agocytosis.