GRO family chemokines are specialized for monocyte arrest from flow

David F. Smith, Elena Galkina, Klaus Ley, Yuqing Huo

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

Chemokines participate in various processes of monocyte recruitment including monocyte arrest and migration. Our group and others have demonstrated that growth-related oncogene (GRO)-α (CXCL1) can support monocyte arrest in models of inflammation. Here we employed a parallel plate-flow chamber and Transwell reconstitution assay to test whether GRO family chemokines were sufficient for Mono Mac 6 (a human monocytic cell line) and isolated human monocyte recruitment. Our study shows that 1) GRO-α, -β (CXCL2), and -7 (CXCL3) all act as arrest chemokines for monocyte adhesion on vascular cell adhesion molecule (VCAM)-1 under flow in the presence of P-selectin; 2) CXCR2 is the functional receptor for GRO-family chemokines in monocyte arrest; however, CXCR2 is not an arrest chemokine receptor in general, since epithelial neutrophil-activating peptide ENA-78 failed to arrest monocytes; 3) GRO-α, -β, and -γ all fail to increase intracellular free Ca2+ or mediate monocyte chemotaxis; and 4) signaling through Gαi protein, phosphoinositide 3-kinase, and actin polymerization but not Ca 2+ mobilization or the mitogen-activated kinases p38 and MAPK/extracellular signal-related kinase are necessary for GRO-α-mediated Mono Mac 6 cell arrest under flow. We conclude that the GRO-family chemokines are specialized monocyte-arrest chemokines. Their role in monocyte recruitment in inflammation can be inhibited by blocking CXCR2 function or downstream signaling events.

Original languageEnglish (US)
Pages (from-to)H1976-H1984
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume289
Issue number5 58-5
DOIs
StatePublished - Nov 1 2005
Externally publishedYes

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Keywords

  • G protein
  • Growth-related oncogene
  • P-selectin
  • Phosphoinositide 3-kinase
  • Signaling
  • Vascular cell adhesion molecule-1

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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