GRO family chemokines are specialized for monocyte arrest from flow

Am J Physiol Heart Circ Physiol. 2005 Nov;289(5):H1976-84. doi: 10.1152/ajpheart.00153.2005. Epub 2005 Jun 3.


Chemokines participate in various processes of monocyte recruitment including monocyte arrest and migration. Our group and others have demonstrated that growth-related oncogene (GRO)-alpha (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-alpha, -beta (CXCL2), and -gamma (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-alpha, -beta, and -gamma all fail to increase intracellular free Ca2+ or mediate monocyte chemotaxis; and 4) signaling through G alpha(i) protein, phosphoinositide 3-kinase, and actin polymerization but not Ca2+ mobilization or the mitogen-activated kinases p38 and MAPK/extracellular signal-related kinase are necessary for GRO-alpha-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / physiology
  • Atherosclerosis / pathology
  • Calcium / metabolism
  • Calcium Signaling / physiology
  • Chemokine CXCL1
  • Chemokines, CXC / physiology*
  • Chemotaxis, Leukocyte / physiology
  • GTP-Binding Protein alpha Subunits, Gi-Go / physiology
  • Humans
  • In Vitro Techniques
  • Indicators and Reagents
  • Inflammation / pathology
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Monocytes / pathology*
  • P-Selectin / metabolism
  • Phosphatidylinositol 3-Kinases / physiology
  • Vascular Cell Adhesion Molecule-1 / metabolism


  • Actins
  • CXCL1 protein, human
  • Chemokine CXCL1
  • Chemokines, CXC
  • Indicators and Reagents
  • Intercellular Signaling Peptides and Proteins
  • P-Selectin
  • Vascular Cell Adhesion Molecule-1
  • Phosphatidylinositol 3-Kinases
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Calcium