A leukocyte homologue of the IL-8 receptor CXCR-2 mediates the accumulation of macrophages in atherosclerotic lesions of LDL receptor-deficient mice

J Clin Invest. 1998 Jan 15;101(2):353-63. doi: 10.1172/JCI1195.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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


  • CXCL1 protein, human
  • Chemokine CXCL1
  • Chemokines, CXC
  • Chemotactic Factors
  • Cxcl1 protein, mouse
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • Receptors, Chemokine
  • Receptors, Interleukin
  • Receptors, Interleukin-8B
  • Receptors, LDL
  • Cholesterol