title: GRO family chemokines are specialized for monocyte arrest from flow.
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)-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.
authors.affiliation: Department of Molecular Physiology, University of Virginia, Charlottesville, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Smith
authors.forename: Elena
authors.initials: E
authors.lastname: Galkina
authors.forename: Klaus
authors.initials: K
authors.lastname: Ley
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Huo
mesh_terms: D000199:Actins / Q000502:physiology; D050197:Atherosclerosis / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007249:Inflammation / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D009000:Monocytes / Q000473:pathology*; D019007:P-Selectin / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000199:Actins; C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D007202:Indicators and Reagents; D036341:Intercellular Signaling Peptides and Proteins; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D019869:Phosphatidylinositol 3-Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D002118:Calcium