TY - JOUR
T1 - The chemokine KC, but not monocyte chemoattractant protein-1, triggers monocyte arrest on early atherosclerotic endothelium
AU - Huo, Yuqing
AU - Weber, Christian
AU - Forlow, S. B.
AU - Sperandio, Markus
AU - Thatte, Jayant
AU - Mack, Matthias
AU - Jung, Steffen
AU - Littman, Dan R.
AU - Ley, Klaus
PY - 2001
Y1 - 2001
N2 - 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-α) 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 α4β1 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.
AB - 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-α) 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 α4β1 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.
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U2 - 10.1172/JCI12877
DO - 10.1172/JCI12877
M3 - Article
C2 - 11696575
AN - SCOPUS:0035189760
SN - 0021-9738
VL - 108
SP - 1307
EP - 1314
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 9
ER -