Manifestations of inflammatory arthritis are critically dependent on LFA-1

Gerald M. Watts, Frank J M Beurskens, Ines Martin-Padura, Christie M. Ballantyne, Lloyd B. Klickstein, Michael B. Brenner, David M. Lee

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Abstract

Leukocyte infiltration of synovial fluid and tissues is the hallmark of inflammatory arthritis. Selectins and β2 integrins have been implicated in the multistep process of leukocyte adhesion to vascular endothelium. However, previous work has revealed disparate requirements for leukocyte recruitments to specific anatomic locales. Moreover, the mechanisms regulating recruitment of leukocytes to the joint in inflammatory arthritis models are not fully understood. We hypothesized that β2 integrins, expressed on leukocytes, might play a pathogenic role in synovial inflammation. Using mice deficient in all β2 integrins (CD18 null mice), we demonstrate that expression of these heterodimeric adhesion molecules is critical for arthritis induction in the K/B x N serum transfer model. Using null-allele mice and blocking mAbs, we demonstrate specifically that CD11a/CD18 (LFA-1) is absolutely required for the development of arthritis in this model. Blocking mAbs further revealed an ongoing requirement for LFA-1 I-domain adhesive function in disease perpetuation. These findings suggest that the LFA-1 I-domain forms an attractive target for treatment of human inflammatory arthritis.

Original languageEnglish
Pages (from-to)3668-3675
Number of pages8
JournalJournal of Immunology
Volume174
Issue number6
Publication statusPublished - Mar 15 2005

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Lymphocyte Function-Associated Antigen-1
Arthritis
Leukocytes
Integrins
Selectins
Synovial Fluid
Vascular Endothelium
Adhesives
Joints
Alleles
Inflammation
Serum

ASJC Scopus subject areas

  • Immunology

Cite this

Watts, G. M., Beurskens, F. J. M., Martin-Padura, I., Ballantyne, C. M., Klickstein, L. B., Brenner, M. B., & Lee, D. M. (2005). Manifestations of inflammatory arthritis are critically dependent on LFA-1. Journal of Immunology, 174(6), 3668-3675.

Manifestations of inflammatory arthritis are critically dependent on LFA-1. / Watts, Gerald M.; Beurskens, Frank J M; Martin-Padura, Ines; Ballantyne, Christie M.; Klickstein, Lloyd B.; Brenner, Michael B.; Lee, David M.

In: Journal of Immunology, Vol. 174, No. 6, 15.03.2005, p. 3668-3675.

Research output: Contribution to journalArticle

Watts, GM, Beurskens, FJM, Martin-Padura, I, Ballantyne, CM, Klickstein, LB, Brenner, MB & Lee, DM 2005, 'Manifestations of inflammatory arthritis are critically dependent on LFA-1', Journal of Immunology, vol. 174, no. 6, pp. 3668-3675.
Watts GM, Beurskens FJM, Martin-Padura I, Ballantyne CM, Klickstein LB, Brenner MB et al. Manifestations of inflammatory arthritis are critically dependent on LFA-1. Journal of Immunology. 2005 Mar 15;174(6):3668-3675.
Watts, Gerald M. ; Beurskens, Frank J M ; Martin-Padura, Ines ; Ballantyne, Christie M. ; Klickstein, Lloyd B. ; Brenner, Michael B. ; Lee, David M. / Manifestations of inflammatory arthritis are critically dependent on LFA-1. In: Journal of Immunology. 2005 ; Vol. 174, No. 6. pp. 3668-3675.
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