Recognition and phagocytosis of apoptotic T cells by resident murine tissue macrophages require multiple signal transduction events.
Macrophages (Mø) ingest apoptotic cells with unique effects on their cytokine production, but the signaling pathways involved are virtually unknown. Signal transduction in response to recognition of apoptotic thymocytes by resident murine alveolar (AMø) or peritoneal (PMø) Mø was studied by in vitro phagocytosis assay. Phagocytosis was decreased in a dose-dependent and nontoxic manner by inhibiting phosphatidylinositol 3 kinase (wortmannin and LY294002), protein tyrosine phosphorylation (herbimycin A, genistein, piceatannol, and for AMø only, PP2), and protein kinase C (staurosporine, Gö 6976, and calphostin C). Exposure of Mø to apoptotic or heat-killed thymocytes, but not to viable thymocytes, activated ERK1/2 rapidly, as detected by specific phosphorylation, but did not activate NF-kappaB or MAP kinases p38 or JNK. Mø phagocytosis of apoptotic T cells requires tyrosine, serine/threonine, and lipid phosphorylation. Mø recognition of apoptotic T cells triggers rapid but limited MAP kinase activation.
Hu
Bin
B
Division of Pulmonary & Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA.
Punturieri
Antonello
A
Todt
Jill
J
Sonstein
Joanne
J
Polak
Timothy
T
Curtis
Jeffrey L
JL
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008264:Macrophages / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011961:Receptors, Fc / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011961:Receptors, Fc; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases