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PMID: 9435307 Published · ppublish English Journal Article 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.

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

The Journal of clinical investigation ·Vol. 101 ·No. 2 ·1998-01-15 ·Pages 353-63

Boisvert WA, Santiago R, Curtiss LK, Terkeltaub RA

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.

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,physiology Receptors, Interleukin/analysis,physiology Receptors, Interleukin-8B Receptors, LDL/deficiency
Chemicals
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
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Boisvert W A
The Scripps Research Institute, La Jolla, California 92037, USA.
Santiago R
Curtiss L K
Terkeltaub R A
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI1195
Published
1998-01-15
Pages
353-63
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC508574
Subset
IM
Grants
NIA NIH HHS · AG-07996 · United States
NHLBI NIH HHS · HL-35297 · United States
NHLBI NIH HHS · HL-57934 · United States
External Links
PubMed source DOI: 10.1172/JCI1195 PMC Full Text View journal details
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