The inhibitory receptor PIR-B negatively regulates neutrophil and macrophage integrin signaling

Shalini Pereira, Hong Zhang, Toshiyuki Takai, Clifford A. Lowell

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)

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 integral-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-α. The pir-b-/- and wild-type cells responded equivalently when stimulated with TNF-α 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 β2 integrins. Biochemical analysis of macrophages 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.

Original languageEnglish
Pages (from-to)5757-5765
Number of pages9
JournalJournal of Immunology
Volume173
Issue number9
DOIs
Publication statusPublished - 2004 Nov 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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