Phospholipase cbeta is critical for T cell chemotaxis. Academic Article Article uri icon

Overview

MeSH

  • Animals
  • Chemokine CXCL12
  • Chemokines
  • Chemokines, CXC
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Mice
  • Mice, Knockout
  • Mutation
  • Neutrophils
  • Phosphatidylinositol 3-Kinases
  • Phospholipase C beta
  • Receptors, Chemokine

MeSH Major

  • Calcium Signaling
  • Chemotaxis
  • Isoenzymes
  • T-Lymphocytes
  • Type C Phospholipases

abstract

  • Chemokines acting through G protein-coupled receptors play an essential role in the immune response. PI3K and phospholipase C (PLC) are distinct signaling molecules that have been proposed in the regulation of chemokine-mediated cell migration. Studies with knockout mice have demonstrated a critical role for PI3K in G(alphai) protein-coupled receptor-mediated neutrophil and lymphocyte chemotaxis. Although PLCbeta is not essential for the chemotactic response of neutrophils, its role in lymphocyte migration has not been clearly defined. We compared the chemotactic response of peripheral T cells derived from wild-type mice with mice containing loss-of-function mutations in both of the two predominant lymphocyte PLCbeta isoforms (PLCbeta2 and PLCbeta3), and demonstrate that loss of PLCbeta2 and PLCbeta3 significantly impaired T cell migration. Because second messengers generated by PLCbeta lead to a rise in intracellular calcium and activation of PKC, we analyzed which of these responses was critical for the PLCbeta-mediated chemotaxis. Intracellular calcium chelation decreased the chemotactic response of wild-type lymphocytes, but pharmacologic inhibition of several PKC isoforms had no effect. Furthermore, calcium efflux induced by stromal cell-derived factor-1alpha was undetectable in PLCbeta2beta3-null lymphocytes, suggesting that the migration defect is due to the impaired ability to increase intracellular calcium. This study demonstrates that, in contrast to neutrophils, phospholipid second messengers generated by PLCbeta play a critical role in T lymphocyte chemotaxis.

publication date

  • August 15, 2007

has subject area

  • Animals
  • Calcium Signaling
  • Chemokine CXCL12
  • Chemokines
  • Chemokines, CXC
  • Chemotaxis
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Isoenzymes
  • Mice
  • Mice, Knockout
  • Mutation
  • Neutrophils
  • Phosphatidylinositol 3-Kinases
  • Phospholipase C beta
  • Receptors, Chemokine
  • T-Lymphocytes
  • Type C Phospholipases

Research

keywords

  • Comparative Study
  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3228861

PubMed ID

  • 17675482

Additional Document Info

start page

  • 2223

end page

  • 2227

volume

  • 179

number

  • 4