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A leukocyte homologue of the il-8 receptor cxcr-2 mediates the accumulation of macrophages in atherosclerotic lesions of ldl receptor-deficient mice

Academic Article
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Overview

authors

  • Boisvert, W. A.
  • Santiago, R.
  • Curtiss, Linda
  • Terkeltaub, R. A.

publication date

  • January 1998

journal

  • Journal of Clinical Investigation  Journal

abstract

  • Chronic macrophage-mediated inflammation is central to atherosclerosis. A role of the monocyte chemotactic and activating C-C chemokine JE/monocyte chemotactic protein-1 has been proposed. However, the human C-X-C chemokines growth-regulated oncogene (GROalpha) and IL-8, and their shared receptor, CXCR-2, also can be expressed at sites of chronic inflammation. Because we detected CXCR-2 in the intima of human atherosclerotic lesions, we examined the role of leukocyte CXCR-2 expression in affecting lesion cellularity. Atherosclerosis-susceptible LDL receptor-deficient mice were irradiated, successfully repopulated with bone marrow cells that either lacked or expressed mIL-8RH (the homologue of CXCR-2), and fed an atherogenic diet for 16 wk. In recipients of mIL-8RH+/+ marrow, mIL-8RH colocalized with densely accumulated intimal MOMA-2 positive macrophages. In contrast, lesions in recipients of mIL-8RH-/- marrow lacked mIL-8RH, had little intimal MOMA-2 staining, and were less extensive. The mIL-8RH ligand KC/GROalpha was detected in the intima of all aortic atherosclerotic lesions. Thus, the capacity of leukocytes to express mIL-8RH, and associated intralesional expression of its ligands such as KC/GROalpha, mediated the intimal accumulation of macrophages in atherosclerotic lesions of LDL receptor-deficient mice.

subject areas

  • Animals
  • Arteriosclerosis
  • Bone Marrow Transplantation
  • Chemokine CXCL1
  • Chemokines, CXC
  • Chemotactic Factors
  • Cholesterol
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • Macrophages
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils
  • Receptors, Chemokine
  • Receptors, Interleukin
  • Receptors, Interleukin-8B
  • Receptors, LDL
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Research

keywords

  • GRO alpha
  • atherogenesis
  • bone marrow transplantation
  • chemokines
  • inflammation
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Identity

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/jci1195

PubMed ID

  • 9435307
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Additional Document Info

start page

  • 353

end page

  • 363

volume

  • 101

issue

  • 2

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