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PMID: 15277234 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Loss of LFA-1, but not Mac-1, protects MRL/MpJ-Fas(lpr) mice from autoimmune disease.

The American journal of pathology ·Vol. 165 ·No. 2 ·2004-08-00 ·Pages 609-16

Kevil CG, Hicks MJ, He X, Zhang J, Ballantyne CM, Raman C, Schoeb TR, Bullard DC

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune complex-mediated tissue injury. Many different adhesion molecules are thought to participate in the development of SLE; however, few studies have directly examined the contributions of these proteins. Here we demonstrate that LFA-1 plays an essential role in the development of lupus in MRL/MpJ-Fas(lpr) mice. Mice deficient in LFA-1, but not Mac-1, showed significantly increased survival, decreased anti-DNA autoantibody formation, and reduced glomerulonephritis. The phenotype of the LFA-1-deficient mice was similar to that observed in beta(2) integrin-deficient (CD18-null) MRL/MpJ-Fas(lpr) mice, suggesting a lack of redundancy among the beta(2) integrin family members and other adhesion molecules. These studies identify LFA-1 as a key contributor in the pathogenesis of autoimmune disease in this model, and further suggest that therapeutic strategies targeting this adhesion molecule may be beneficial for the treatment of SLE.

MeSH Terms
Animals Autoantibodies/analysis CD11 Antigens/metabolism CD18 Antigens/metabolism Glomerulonephritis/prevention & control Kidney Function Tests Lupus Erythematosus, Systemic/pathology,prevention & control Lymphatic Diseases/prevention & control Lymphocyte Function-Associated Antigen-1/metabolism Macrophage-1 Antigen/metabolism Mice Mice, Inbred C57BL Mice, Inbred MRL lpr Mice, Knockout
Chemicals
Autoantibodies CD11 Antigens CD18 Antigens Lymphocyte Function-Associated Antigen-1 Macrophage-1 Antigen
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Kevil Christopher G
Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
Hicks M John
He Xiaodong
Zhang Junxuan
Ballantyne Christie M
Raman Chander
Schoeb Trenton R
Bullard Daniel C
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)63325-1
Published
2004-08-00
Pages
609-16
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1618580
Subset
IM
Grants
NIA NIH HHS · R01 AG016221 · United States
NCRR NIH HHS · R01 RR017009 · United States
NIAID NIH HHS · T32 AI007051 · United States
NCRR NIH HHS · RR-017009 · United States
External Links
PubMed source DOI: 10.1016/S0002-9440(10)63325-1 PMC Full Text View journal details
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