The critical role of intercellular adhesion molecule-1 in Masugi nephritis in rats.
The critical role of intercellular adhesion molecule-1 in Masugi nephritis in rats.
复制标题
细胞间粘附分子1在大鼠Masugi肾炎中的关键作用。
作者：
J. Wada;K. Shikata;H. Makino;S. Morioka;K. Hirata;K. Ota;T. Tamatani;M. Miyasaka;T. Horiuchi;S. Noji;K. Nishikawa;F. Myokai;S. Taniguchi;Y. Kanwar;Z. Ota
细胞间粘附分子-1（ICAM-1，CD54）是免疫球蛋白超家族的一种粘附分子，是淋巴细胞功能相关分子1（LFA-1，CD11a/CD18）、Mac-1（CD11b/CD18）和CD43等白细胞整合素的内皮细胞表面配体。这些分子介导白细胞和内皮细胞之间的粘附相互作用，并在白细胞浸润到炎性病变中起关键作用。我们检测了Masugi肾炎大鼠肾组织中ICAM-1的表达，并通过给予大鼠ICAM-1、LFA-1 α-亚基（LFA-1 α）、β-亚基（LFA-1 β）和Mac-1 α-亚基（Mac-1 α）的中和性单克隆抗体（MAbs）直接检测了ICAM-1的作用。在注射肾毒血清后3小时内，通过原位杂交和免疫荧光研究检测到肾小球中ICAM-1的表达增加。抗ICAM-1、Mac-1 α和LFA-1 β的单克隆抗体显著抑制蛋白尿。通过注射抗ICAM-1、LFA-1 α和LFA-1 β的单克隆抗体，显著防止了神经元浸润到肾小球中。这些结果表明ICAM-1/LFA-1和ICAM-1/Mac-1途径都参与了中性粒细胞向肾小球的浸润。另一方面，抗ICAM-1、LFA-1 α和LFA-1 β的单克隆抗体可防止单核细胞浸润，但抗Mac-1 α单克隆抗体则不能。由于这些结果，ICAM-1被认为是参与Masugi肾炎异源期白细胞浸润到肾小球中的发病机制的关键分子。抗ICAM-1抗体可能对白细胞介导的肾小球疾病的治疗有益。
Intercellular adhesion molecule-1 (ICAM-1, CD54), an adhesion molecule of the immunoglobulin superfamily, is an endothelial cell surface ligand for such leukocyte integrins as lymphocyte-function-associated molecule 1 (LFA-1, CD11a/CD18), Mac-1 (CD11b/CD18) and CD43. These molecules mediate adhesive interactions between leukocytes and endothelial cells and are critically involved in infiltration of leukocytes into inflammatory lesions. We examined the expression of ICAM-1 in renal tissues of Masugi nephritis rats and directly examined the role of ICAM-1 by administration of neutralizing monoclonal antibodies (MAbs) to rat ICAM-1, LFA-1 alpha-subunit (LFA-1 alpha), beta-subunit (LFA-1 beta) and Mac-1 alpha-subunit (Mac-1 alpha). Within 3 h after injection of nephrotoxic serum, increased expression of ICAM-1 was detected in the glomeruli by in situ hybridization and an immunofluorescence study. Proteinuria was significantly suppressed by the MAbs against ICAM-1, Mac-1 alpha and LFA-1 beta. Neutrophil infiltration into the glomeruli was significantly prevented by injection of the MAbs against ICAM-1, LFA-1 alpha and LFA-1 beta. These results indicate that both ICAM-1/LFA-1 and ICAM-1/Mac-1 pathways are involved in neutrophil infiltration into the glomeruli. On the other hand, monocytic infiltration was prevented by the MAbs against ICAM-1, LFA-1 alpha and LFA-1 beta but not by anti-Mac-1 alpha MAb. Due to these results, ICAM-1 is considered to be a critical molecule involved in the pathogenesis of the leukocyte infiltration into the glomeruli in the heterologous phase of Masugi nephritis. Anti-ICAM-1 antibody may be beneficial in the treatment of leukocyte-mediated glomerular diseases.