Activation of Protein Kinase C βII by the Stereo-specific Phosphatidylserine Receptor Is Required for Phagocytosis of Apoptotic Thymocytes by Resident Murine Tissue Macrophages

• Published in: The Journal of biological chemistry 2002-09, Vol.277 (39), p.35906-35914
• Main Authors: Todt, Jill C., Hu, Bin, Punturieri, Antonello, Sonstein, Joanne, Polak, Timothy, Curtis, Jeffrey L.
• Format: Article
• Language: English
• Subjects: Acetophenones - pharmacology; Animals; Apoptosis; Benzopyrans - pharmacology; Blotting, Western; Cell Adhesion; Dose-Response Relationship, Drug; Enzyme Activation; Female; Flow Cytometry; Immunoblotting; Indoles - pharmacology; Inhibitory Concentration 50; Isoenzymes - metabolism; Liposomes - metabolism; Macrophages - metabolism; Mice; Mice, Inbred C57BL; Myristic Acid - pharmacology; Phagocytosis; Protein Isoforms; Protein Kinase C - chemistry; Protein Kinase C - metabolism; Protein Kinase C beta; Protein Transport; Pyrroles - pharmacology; Receptors, Cell Surface - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA - metabolism; Tetradecanoylphorbol Acetate - pharmacology; Thymus Gland - cytology; Time Factors
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M202967200

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