Brief cross-linking of Fas/APO-1 (CD95) triggers engulfment of pre-apoptotic target cells.
Macrophage clearance of dying cells is of crucial importance to maintain tissue homeostasis. Here, we show that brief treatment (15min) of Jurkat T cells with agonistic anti-Fas antibodies or recombinant Fas ligand results in efficient phagocytosis by human monocyte-derived macrophages prior to the occurrence of common biomarkers of apoptosis. Similar findings were obtained when using primary human T cells. Macrophage engulfment of pre-apoptotic target cells was suppressed in the absence of serum. Moreover, pre-apoptotic cells secreted annexin I and administration of Boc1, a formyl peptide receptor/lipoxin receptor antagonist markedly attenuated their engulfment. Finally, pre-apoptotic Jurkat cells induced lower macrophage production of tumor necrosis factor-alpha and higher production of interleukin-10 in comparison to apoptotic target cells.
Zhang
Shouting
S
Cell Death Research Group, Division of Biochemical Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden.
Witasp
Erika
E
Lauwen
Marjolein
M
Fadeel
Bengt
B
D017305:Annexin A1 / Q000502:physiology; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D053222:Fas Ligand Protein / Q000235:genetics / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D010587:Phagocytosis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019014:fas Receptor / Q000037:antagonists & inhibitors* / Q000276:immunology
D017305:Annexin A1; D000906:Antibodies; D016207:Cytokines; D053222:Fas Ligand Protein; D019014:fas Receptor; D020169:Caspases