A Crucial Role of L‐Selectin in C Protein–Induced Experimental Polymyositis in Mice. Issue 7 (July 2014)

• Record Type: Journal Article
• Authors: Oishi, Kyosuke; Hamaguchi, Yasuhito; Matsushita, Takashi; Hasegawa, Minoru; Okiyama, Naoko; Dernedde, Jens; Weinhart, Marie; Haag, Rainer; Tedder, Thomas F.; Takehara, Kazuhiko; Kohsaka, Hitoshi; Fujimoto, Manabu
• Is Part Of: Arthritis & rheumatology. Volume 66:Issue 7(2014)
• Page Start: 1864
• Page End: 1871
• Publication Date: 2014-07
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; 616.72
• DOI: 10.1002/art.38630
• Languages: English
• ISSNs: 2326-5191

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="art38630-sec-0001" sec-type="section"> <title>Objective</title> <p>To investigate the role of adhesion molecules in C protein–induced myositis (CIM), a murine model of polymyositis (PM).</p> </sec> <sec id="art38630-sec-0002" sec-type="section"> <title>Methods</title> <p>CIM was induced in wild‐type mice, L‐selectin–deficient (L‐selectin<sup>−/−</sup>) mice, intercellular adhesion molecule 1 (ICAM‐1)–deficient (ICAM‐1<sup>−/−</sup>) mice, and mice deficient in both L‐selectin and ICAM‐1 (L‐selectin<sup>−/−</sup>ICAM‐1<sup>−/−</sup> 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.</p> </sec> <sec id="art38630-sec-0003" sec-type="section"> <title>Results</title> <p>L‐selectin<sup>−/−</sup> mice and L‐selectin<sup>−/−</sup>ICAM‐1<sup>−/−</sup> mice developed significantly less severe myositis compared to wild‐type mice, while ICAM‐1 deficiency did not inhibit the development of myositis. L‐selectin<sup>−/−</sup> 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.</p> </sec> <sec id="art38630-sec-0004" sec-type="section"> <title>Conclusion</title> <p>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.</p> </sec> </abstract>