Leppert D, Waubant E, Galardy R, Bunnett N W, Hauser S L
Department of Neurology, University of California at San Francisco 94143, USA.
J Immunol. 1995 May 1;154(9):4379-89.
T cell homing into extravascular sites requires penetration across the subendothelial basal lamina, a specialized nonfibrillar connective tissue structure that anchors endothelial cells to parenchymal surfaces. Herein, we show that normal human T cells express gelatinases A and B, two matrix metalloproteinases active against the major basal lamina constituents, collagen types IV and V. Expression is confirmed at both the mRNA and protein levels. Gelatinase B is expressed constitutively, whereas gelatinases A and B expression is induced by T cell activation. In vitro migration of resting T cells across a basal lamina equivalent is mediated by gelatinase B, because it is specifically blocked by GM6001, a hydroxamic acid inhibitor of matrix metalloproteinases. Inhibition of T cell homing by interference with gelatinase function may represent a useful approach to the treatment of T cell-mediated autoimmune diseases.
T细胞归巢至血管外部位需要穿透内皮下基膜，内皮下基膜是一种特殊的非纤维性结缔组织结构，可将内皮细胞锚定在实质表面。在此，我们表明正常人T细胞表达明胶酶A和B，这两种基质金属蛋白酶对主要的基膜成分IV型和V型胶原具有活性。在mRNA和蛋白质水平均证实了其表达。明胶酶B组成性表达，而明胶酶A和B的表达则由T细胞活化诱导。静息T细胞在等效基膜上的体外迁移由明胶酶B介导，因为它被基质金属蛋白酶的异羟肟酸抑制剂GM6001特异性阻断。通过干扰明胶酶功能来抑制T细胞归巢可能是治疗T细胞介导的自身免疫性疾病的一种有用方法。
