Article

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

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0642, USA.
American Journal of Respiratory Cell and Molecular Biology (impact factor: 5.13). 01/2001; 23(6):727-33. pp.727-33
Source: PubMed

ABSTRACT 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.

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Keywords

augmenting rat alveolar macrophage
 
C-opsonized sheep red blood cells
 
complete immune serum
 
deplete PKC
 
Fc receptor
 
FcR)-mediated phagocytosis
 
FcR-mediated phagocytosis
 
heat-inactivated immune serum
 
IgG-opsonized fluorescent microspheres
 
K. pneumoniae opsonized
 
Klebsiella pneumoniae opsonized
 
LT enhancement
 
non-immune serum
 
phorbol 12-myristate 13-acetate
 
PKC activation
 
PKC activity
 
PKC inhibitors staurosporine
 
protein kinase
 
targets opsonized
 
two well-known opsonins