title: Regulation of Phagocyte Migration by Signal Regulatory Protein-Alpha Signaling.
abstract: Signaling through the inhibitory receptor signal regulatory protein-alpha (SIRPα) controls effector functions in phagocytes. However, there are also indications that interactions between SIRPα and its ligand CD47 are involved in phagocyte transendothelial migration. We have investigated the involvement of SIRPα signaling in phagocyte migration in vitro and in vivo using mice that lack the SIRPα cytoplasmic tail. During thioglycolate-induced peritonitis in SIRPα mutant mice, both neutrophil and macrophage influx were found to occur, but to be significantly delayed. SIRPα signaling appeared to be essential for an optimal transendothelial migration and chemotaxis, and for the amoeboid type of phagocyte migration in 3-dimensional environments. These findings demonstrate, for the first time, that SIRPα signaling can directly control phagocyte migration, and this may contribute to the impaired inflammatory phenotype that has been observed in the absence of SIRPα signaling.
authors.affiliation: Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, The Netherlands.
authors.forename: Julian
authors.initials: J
authors.lastname: Alvarez-Zarate
authors.affiliation: Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, The Netherlands.
authors.forename: Hanke L
authors.initials: HL
authors.lastname: Matlung
authors.affiliation: Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matozaki
authors.affiliation: Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, The Netherlands; Emma Children's Hospital, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
authors.affiliation: Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, The Netherlands; CNRS, UMR5089, IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse, France; Université de Toulouse, UPS, IPBS, Toulouse, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Maridonneau-Parini
authors.affiliation: Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, The Netherlands.
authors.forename: Timo K
authors.initials: TK
authors.lastname: van den Berg
mesh_terms: D000818:Animals; D002465:Cell Movement; D002633:Chemotaxis; D005109:Extracellular Matrix / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology; D008810:Mice, Inbred C57BL; D010538:Peritonitis / Q000378:metabolism / Q000473:pathology; D010586:Phagocytes / Q000166:cytology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction; D013864:Thioglycolates
chemical_list: C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic; D013864:Thioglycolates; C017487:2-mercaptoacetate