Basal activation of protein kinase C in rat alveolar macrophages: implications for arachidonate metabolism.
Alveolar macrophages (AM) exhibit numerous functional differences from other mononuclear phagocyte populations, even though they are derived from a common circulating monocytic precursor. Yet no differences in fundamental signaling mechanisms uniquely expressed by AM have been elucidated to date. Protein kinase C (PKC) is one signal transduction mechanism thought to have an important role in regulating macrophage function and about which little information exists for AM. This study was undertaken to assess the state of activation of PKC in cultured resident rat AM compared with resident rat peritoneal macrophages (PM) and the means by which active PKC regulates arachidonic acid (AA) metabolism in the two cell types. As assessed by a histone phosphorylation assay, resting AM, in contrast to PM, exhibited constitutive activation of PKC as evidenced by localization of a majority of PKC activity to the membrane fraction. Ionophore A23187-stimulated release and metabolism of AA were attenuated by depletion of or inhibition of cellular PKC activity in AM but not in PM. In contrast, A23187-stimulated AA metabolism was augmented by activation of PKC to a greater extent in PM than in AM. Results from both cell types indicated that the 5-lipoxygenase pathway was particularly upregulated by PKC activation. We conclude that activation of PKC occurs uniquely during macrophage residence in the alveolar space and that this property as well as the downregulation of PKC which results have profound consequences for the regulation of at least one important macrophage function, the synthesis of bioactive eicosanoids.
Peters-Golden
M
M
Department of Internal Medicine, University of Michigan, Ann Arbor.
McNish
R W
RW
Sporn
P H
PH
Balazovich
K
K
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D001481:Basal Metabolism; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D004789:Enzyme Activation; D005260:Female; D007975:Leukotriene B4 / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology / Q000201:enzymology*; D010537:Peritoneum; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D000470:Alkaloids; D001095:Arachidonic Acids; D007975:Leukotriene B4; D000001:Calcimycin; D015054:Zymosan; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate