Macrophage recognition of ICAM-3 on apoptotic leukocytes.
Cells undergoing apoptosis are cleared rapidly by phagocytes, thus preventing tissue damage caused by loss of plasma membrane integrity. In this study, we show that the surface of leukocytes is altered during apoptosis such that the first Ig-like domain of ICAM-3 (CD50) can participate in the recognition and phagocytosis of the apoptotic cells by macrophages. Macrophage recognition of apoptotic cell-associated ICAM-3 was demonstrated both on leukocytes and, following transfection of exogenous ICAM-3, on nonleukocytes. The change in ICAM-3 was a consistent consequence of apoptosis triggered by various stimuli, suggesting that it occurs as part of a final common pathway of apoptosis. Alteration of ICAM-3 on apoptotic cells permitting recognition by macrophages resulted in a switch in ICAM-3-binding preference from the prototypic ICAM-3 counterreceptor, LFA-1, to an alternative macrophage receptor. Using mAbs to block macrophage/apoptotic cell interactions, we were unable to obtain evidence that either the alternative ICAM-3 counterreceptor alpha d beta 2 or the apoptotic cell receptor alpha v beta 3 was involved in the recognition of ICAM-3. By contrast, mAb blockade of macrophage CD14 inhibited ICAM-3-dependent recognition of apoptotic cells. These results show that ICAM-3 can function as a phagocytic marker of apoptotic leukocytes on which it acquires altered macrophage receptor-binding activity.
Moffatt
O D
OD
Institute of Cell Signaling, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, United Kingdom.
Devitt
A
A
Bell
E D
ED
Simmons
D L
DL
Gregory
C D
CD
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D000943:Antigens, Differentiation; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D002051:Burkitt Lymphoma; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D002450:Cell Communication / Q000276:immunology*; D002460:Cell Line; D018920:Coculture Techniques; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007668:Kidney / Q000166:cytology; D007962:Leukocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D010449:Peptide Mapping; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; D018985:Epitopes, B-Lymphocyte; C483616:ICAM3 protein, human; D007166:Immunosuppressive Agents