ucn-1028-c and zileuton

We have previously established an important role for leukotrienes (LTs) in augmenting rat alveolar macrophage (AM) phagocytosis of Klebsiella pneumoniae opsonized with complete immune serum (IS), which contains the two well-known opsonins, immunoglobulin (Ig) G and complement (C). In this report, the specific opsonin requirements for LT modulation of AM phagocytosis and the dependence of this response on protein kinase (PK) C activity were investigated. Phagocytosis of K. pneumoniae opsonized with IS, non-immune serum, or heat-inactivated immune serum and of inert targets (IgG-opsonized fluorescent microspheres or C-opsonized sheep red blood cells) was examined. Inhibition of endogenous LT synthesis or action attenuated, whereas the addition of exogenous LTs augmented, phagocytosis only of targets opsonized with IgG. LTs had no effect on phagocytosis of C-opsonized or unopsonized targets. LTs did not affect adherence of IgG-opsonized targets, implying instead an 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 LTB(4) and largely inhibited the ability of LTC(4) to augment phagocytosis of IgG-opsonized microspheres. These results demonstrate that LT enhancement is confined to Fc receptor (FcR)-mediated phagocytosis. Moreover, PKC activation represents an important mechanism by which LTs promote FcR-mediated phagocytosis.

Topics: Acetophenones; Animals; Cell Line; Dose-Response Relationship, Drug; Enzyme Inhibitors; Erythrocytes; Female; Hydroxyurea; Immune Sera; Immunoglobulin G; Klebsiella pneumoniae; Leukotriene Antagonists; Leukotrienes; Macrophages, Alveolar; Microspheres; Naphthalenes; Phagocytosis; Protein Kinase C; Rats; Rats, Wistar; Receptors, Cell Surface; Receptors, Fc; Receptors, Leukotriene B4; Sheep; Staurosporine; Tetradecanoylphorbol Acetate; Tetrazoles