Manifestations of inflammatory dependent on LFA-1
Manifestations of inflammatory dependent on LFA-1
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DOI：
10.4049/jimmunol.174.6.3668
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发表时间：
2005-03-15
影响因子：
4.4
通讯作者：
Lee, DM
中科院分区：
文献类型：
--
作者：
Watts, GM;Beurskens, FJM;Lee, DM
Leukocyte infiltration of synovial fluid and tissues is the hallmark of inflammatory arthritis. Selectins and 13, 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 13, integrins, expressed on leukocytes, might play a pathogenic role in synovial inflammation. Using mice deficient in all 0, 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. The Journal of Immunology, 2005, 174: 3668-3675.
