title: The inhibitory receptor PIR-B negatively regulates neutrophil and macrophage integrin signaling.
abstract: The Ig-like receptor family member, PIR-B, has been shown to play an inhibitory role in receptor signaling within B cells, mast cells, and dendritic cells. As it has been implicated in integrin-mediated responses, we investigated the effect of loss of the PIR-B protein on integrin-mediated signaling in primary murine myeloid cells. The pir-b-/- neutrophils displayed enhanced respiratory burst, secondary granule release, and a hyperadhesive phenotype when plated on surfaces coated with either extracellular matrix proteins or cellular adhesion molecules in the presence or absence of the soluble inflammatory agonist TNF-alpha. The pir-b-/- and wild-type cells responded equivalently when stimulated with TNF-alpha in suspension, indicating that the hyperresponsive phenotype of the pir-b-/- cells during adhesion was due to enhanced integrin signaling. Both wild-type and pir-b-/- neutrophils expressed similar levels of integrin subunits. Primary bone marrow-derived macrophages from pir-b-/- mice were also hyperadhesive and spread more rapidly than wild-type cells following plating on surfaces that cross-linked cellular beta2 integrins. Biochemical analysis of macrophages from pir-b-/- mice revealed enhanced phosphorylation and activation of proteins involved in integrin signaling. These observations point to a nonredundant role for PIR-B in the regulation of leukocyte integrin signaling.
authors.affiliation: Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA.
authors.forename: Shalini
authors.initials: S
authors.lastname: Pereira
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takai
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Lowell
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D007424:Intracellular Fluid / Q000276:immunology / Q000502:physiology; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D003432:Cross-Linking Reagents; D016023:Integrins; C105949:Pirb protein, mouse; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D009240:N-Formylmethionine Leucyl-Phenylalanine