The chemokine KC, but not monocyte chemoattractant protein-1, triggers monocyte arrest on early atherosclerotic endothelium

Yuqing Huo, Christian Weber, S. B. Forlow, Markus Sperandio, Jayant Thatte, Matthias Mack, Steffen Jung, Dan R. Littman, Klaus Ley

Research output: Contribution to journalArticle

232 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1307-1314
Number of pages8
JournalJournal of Clinical Investigation
Volume108
Issue number9
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    Huo, Y., Weber, C., Forlow, S. B., Sperandio, M., Thatte, J., Mack, M., Jung, S., Littman, D. R., & Ley, K. (2001). The chemokine KC, but not monocyte chemoattractant protein-1, triggers monocyte arrest on early atherosclerotic endothelium. Journal of Clinical Investigation, 108(9), 1307-1314. https://doi.org/10.1172/JCI12877