Kramer M D, Reinartz J
University Institute for Immunology and Serology, Laboratory of Immunopathology, Heidelberg, Germany.
J Clin Invest. 1993 Aug;92(2):978-83. doi: 10.1172/JCI116674.
Plasminogen activators produced locally in the skin have been implicated in blistering skin diseases. To explore whether plasminogen activators convert their substrate plasminogen into plasmin locally in the lesional skin we have analyzed the autoimmune blistering skin disease bullous pemphigoid. Enzyme activity was detected in bullous pemphigoid skin blister fluid by using a low molecular weight chromogenic substrate for plasmin. Enzyme activity was detected neither in suction blister fluid raised on normal skin nor in normal plasma. Immunoprecipitation or fractionation by molecular sieve chromatography of bullous pemphigoid skin blister fluid followed by testing in immunoassays disclosed putative plasmin/alpha 2-macroglobulin complexes and plasmin/alpha 2-antiplasmin complexes. Enzyme activity detected in bullous pemphigoid skin blister fluid by the low molecular weight chromogenic peptide assay was ascribed to the putative plasmin pha 2-macroglobulin complexes. Because formation of plasmin-inhibitor complexes requires the active plasmin, our findings indicate previous activation of plasminogen to plasmin in skin lesions. There was no evidence for free plasmin (i.e., plasmin not complexed to inhibitors) in bullous pemphigoid blister fluid, suction blister fluid, or plasma.
皮肤局部产生的纤溶酶原激活剂与水疱性皮肤病有关。为了探究纤溶酶原激活剂是否在皮损局部将其底物纤溶酶原转化为纤溶酶，我们分析了自身免疫性水疱性皮肤病大疱性类天疱疮。通过使用纤溶酶的低分子量显色底物，在大疱性类天疱疮皮肤疱液中检测到了酶活性。在正常皮肤产生的吸引疱液或正常血浆中均未检测到酶活性。对大疱性类天疱疮皮肤疱液进行免疫沉淀或分子筛层析分级分离，然后进行免疫分析检测，发现了假定的纤溶酶/α2-巨球蛋白复合物和纤溶酶/α2-抗纤溶酶复合物。通过低分子量显色肽分析法在大疱性类天疱疮皮肤疱液中检测到的酶活性归因于假定的纤溶酶/α2-巨球蛋白复合物。由于纤溶酶-抑制剂复合物的形成需要活性纤溶酶，我们的研究结果表明皮损中纤溶酶原先前已被激活为纤溶酶。在大疱性类天疱疮疱液、吸引疱液或血浆中没有游离纤溶酶（即未与抑制剂结合的纤溶酶）的证据。
