A crucial role of L-selectin in C protein-induced experimental polymyositis in mice.

Journal Article

To investigate the role of adhesion molecules in C protein-induced myositis (CIM), a murine model of polymyositis (PM).CIM was induced in wild-type mice, L-selectin-deficient (L-selectin(-/-) ) mice, intercellular adhesion molecule 1 (ICAM-1)-deficient (ICAM-1(-/-) ) mice, and mice deficient in both L-selectin and ICAM-1 (L-selectin(-/-) ICAM-1(-/-) mice). Myositis severity, inflammatory cell infiltration, and messenger RNA expression in the inflamed muscles were analyzed. The effect of dendritic polyglycerol sulfate, a synthetic inhibitor that suppresses the function of L-selectin and endothelial P-selectin, was also examined.L-selectin(-/-) mice and L-selectin(-/-) ICAM-1(-/-) mice developed significantly less severe myositis compared to wild-type mice, while ICAM-1 deficiency did not inhibit the development of myositis. L-selectin(-/-) mice that received wild-type T cells developed myositis. Treatment with dendritic polyglycerol sulfate significantly diminished the severity of myositis in wild-type mice compared to treatment with control.These data indicate that L-selectin plays a major role in the development of CIM, whereas ICAM-1 plays a lesser role, if any, in the development of CIM. L-selectin-targeted therapy may be a candidate for the treatment of PM.

Full Text

Duke Authors

Cited Authors

  • Oishi, K; Hamaguchi, Y; Matsushita, T; Hasegawa, M; Okiyama, N; Dernedde, J; Weinhart, M; Haag, R; Tedder, TF; Takehara, K; Kohsaka, H; Fujimoto, M

Published Date

  • July 2014

Published In

Volume / Issue

  • 66 / 7

Start / End Page

  • 1864 - 1871

PubMed ID

  • 24644046

Electronic International Standard Serial Number (EISSN)

  • 2326-5205

International Standard Serial Number (ISSN)

  • 2326-5191

Digital Object Identifier (DOI)

  • 10.1002/art.38630

Language

  • eng