TY - JOUR
T1 - The inhibitory receptor PIR-B negatively regulates neutrophil and macrophage integrin signaling
AU - Pereira, Shalini
AU - Zhang, Hong
AU - Takai, Toshiyuki
AU - Lowell, Clifford A.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2004/11/1
Y1 - 2004/11/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.173.9.5757
DO - 10.4049/jimmunol.173.9.5757
M3 - Article
C2 - 15494528
AN - SCOPUS:6344274703
VL - 173
SP - 5757
EP - 5765
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 9
ER -