title: Novel role of ICAM3 and LFA-1 in the clearance of apoptotic neutrophils by human macrophages.
abstract: Apoptotic cells express eat-me signals which are recognized by several receptors mainly on professional phagocytes of the mononuclear phagocyte system. This "engulfment synapse" can define a safe and effective clearance of apoptotic cells in order to maintain tissue homeostasis in the entire body. We show that the expression of four genes related to apoptotic cell clearance is strongly up-regulated in human macrophages 30 min after administration of apoptotic neutrophils. Out of these the significant role of the up-regulated intercellular adhesion molecule 3 (ICAM3) in phagocytosis of apoptotic neutrophils could be demonstrated in macrophages by gene silencing as well as treatment with blocking antibodies. Blocking ICAM3 on the surface of apoptotic neutrophils also resulted in their decreased uptake which confirmed its role as an eat-me signal expressed by apoptotic cells. In macrophages but not in neutrophils silencing and blocking integrin alphaL and beta2 components of lymphocyte function-associated antigen 1 (LFA-1), which can strongly bind ICAM3, resulted in a decreased phagocytosis of apoptotic cells indicating its possible role to recognize ICAM3 on the surface of apoptotic neutrophils. Finally, we report that engulfing portals formed in macrophages during phagocytosis are characterized by accumulation of ICAM3, integrin alphaL and beta2 which show co-localization on the surface of phagocytes. Furthermore, their simultaneous knock-down in macrophages resulted in a marked deficiency in phagocytosis and a slight decrease in the anti-inflammatory effect of apoptotic neutrophils. We propose that ICAM3 and LFA-1 act as recognition receptors in the phagocytosis portals of macrophages for engulfment of apoptotic neutrophils.
authors.affiliation: Department of Biochemistry and Molecular Biology, Stem Cells, Apoptosis and Genomics Research Group of the Hungarian Academy of Sciences, University of Debrecen, Egyetem Tér 1, Debrecen, 4010, Hungary.
authors.forename: Endre
authors.initials: E
authors.lastname: Kristóf
authors.forename: Gábor
authors.initials: G
authors.lastname: Zahuczky
authors.forename: Klára
authors.initials: K
authors.lastname: Katona
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Doró
authors.forename: Éva
authors.initials: É
authors.lastname: Nagy
authors.forename: László
authors.initials: L
authors.lastname: Fésüs
mesh_terms: D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D017209:Apoptosis / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C483616:ICAM3 protein, human; D016169:Lymphocyte Function-Associated Antigen-1