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 language | English (US) |
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Pages (from-to) | H1976-H1984 |
Journal | American Journal of Physiology - Heart and Circulatory Physiology |
Volume | 289 |
Issue number | 5 58-5 |
DOIs | |
State | Published - Nov 2005 |
Externally published | Yes |
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)