The chemokine KC, but not monocyte chemoattractant protein-1, triggers monocyte arrest on early atherosclerotic endothelium.
In a reconstituted flow chamber system, preincubation with chemokines can trigger the arrest of rolling monocytes, suggesting that this interaction could help recruit these cells to early atherosclerotic lesions. To date, however, the contribution of endothelium-derived chemokines found in these lesion to monocyte arrests has not been investigated. The endothelium of lesion-prone carotid arteries from apolipoprotein E-deficient (ApoE(-/-)) mice, but not control mice, presents the chemokines KC (mouse GRO-alpha) and JE (mouse monocyte chemoattractant protein-1 [MCP-1]). Arrest of a monocytic cell line or mouse blood monocytes perfused through carotid arteries of ApoE(-/-) mice was reduced by treating with either pertussis toxin, an antagonist of CXCR2, or an antibody to KC, but this process was insensitive to agents that blocked CCR-2 or JE. Conversely, monocyte accumulation more than doubled upon pre-perfusion of the carotid artery with KC but not with mouse MCP-1. Blockade of alpha(4)beta(1) integrin (VLA-4) or vascular cell adhesion molecule-1, but not CD18 or intercellular adhesion molecule-1, almost completely inhibited the arrest of monocytes. We conclude that when presented by early atherosclerotic lesions, KC but not murine MCP-1 triggers VLA-4-dependent monocyte recruitment.
Huo
Y
Y
Cardiovascular Research Center and Department of Biomedical Engineering, University of Virginia, Health Science Center, Charlottesville, Virginia 22908, USA.
Weber
C
C
Forlow
S B
SB
Sperandio
M
M
Thatte
J
J
Mack
M
M
Jung
S
S
Littman
D R
DR
Ley
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism*; D018821:CD18 Antigens / Q000378:metabolism; D002339:Carotid Arteries / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism* / Q000502:physiology*; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000378:metabolism* / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism* / Q000502:physiology*; D037342:Pertussis Toxin; D011485:Protein Binding; D051381:Rats; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; C475829:CXCL1 protein, human; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; C513297:Cxcl1 protein, rat; D006133:Growth Substances; D039041:Integrin alpha4beta1; D016023:Integrins; D036341:Intercellular Signaling Peptides and Proteins; D023063:Receptors, Interleukin-8B; D016201:Receptors, Lymphocyte Homing; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin