Schaefer B M, Maier K, Eickhoff U, Bechtel M, Kramer M D
Institut für Immunologie, Universität Heidelberg, Germany.
Arch Dermatol Res. 1996 Mar;288(3):122-8. doi: 10.1007/BF02505820.
Mechanical injury of tissues is followed by the formation of a provisional fibrin matrix, which is later replaced by granulation tissue. The fibrinolytic proteinase, plasmin, is thought to contribute to the displacement of the primary matrix. Plasmin is generated from the ubiquitous proenzyme plasminogen by plasminogen activators. The system of plasminogen activation is controlled at several levels: plasminogen activator inhibitors (PAI-1 and PAI-2) counteract the activity of plasminogen activators and alpha 2-antiplasmin inhibits the activity of plasmin. In order to elucidate the mechanisms that regulate the plasminogen activator system in healing human skin wounds, we performed the immunohistological study reported here. The plasmin inhibitor alpha 2-antiplasmin and PAI-2 were found in the primary fibrin-rich matrix and in the granulation tissue. alpha 2-Antiplasmin was diffusely distributed in the tissue and its distribution correlated with the presence and localization of plasmin(ogen) except that, in contrast to plasmin(ogen), the alpha 2-antiplasmin was apparently not cell-associated. The stainings for PAI-2 increased with time and paralleled the development of the cellular infiltrate. PAI-2 was found in association with cells, which were identified by double immunofluorescence stainings as monocytes/macrophages and fibroblasts. In line with the immunohistological data, polymerase chain reaction after reverse transcription revealed mRNA for PAI-2 in healing human skin wounds. Taken together, our findings indicate that in healing human skin wounds, PAI-2 is the primary regulator of plasminogen activators, whereas alpha 2-antiplasmin may serve to control plasmin activity.
组织受到机械损伤后会形成临时的纤维蛋白基质，随后被肉芽组织取代。纤维蛋白溶解蛋白酶，即纤溶酶，被认为有助于初级基质的替代。纤溶酶由普遍存在的酶原纤溶酶原通过纤溶酶原激活剂生成。纤溶酶原激活系统在多个水平受到调控：纤溶酶原激活剂抑制剂（PAI - 1和PAI - 2）抵消纤溶酶原激活剂的活性，而α2 - 抗纤溶酶抑制纤溶酶的活性。为了阐明在人类皮肤伤口愈合过程中调节纤溶酶原激活系统的机制，我们进行了此处报道的免疫组织学研究。在富含纤维蛋白的初级基质和肉芽组织中发现了纤溶酶抑制剂α2 - 抗纤溶酶和PAI - 2。α2 - 抗纤溶酶在组织中呈弥漫性分布，其分布与纤溶酶（原）的存在和定位相关，不同的是，与纤溶酶（原）相比，α2 - 抗纤溶酶显然不与细胞相关。PAI - 2的染色随时间增加，并与细胞浸润的发展平行。PAI - 2与细胞相关，通过双重免疫荧光染色鉴定这些细胞为单核细胞/巨噬细胞和成纤维细胞。与免疫组织学数据一致，逆转录后的聚合酶链反应显示在人类皮肤伤口愈合过程中有PAI - 2的mRNA。综上所述，我们的研究结果表明，在人类皮肤伤口愈合过程中，PAI - 2是纤溶酶原激活剂的主要调节因子，而α2 - 抗纤溶酶可能用于控制纤溶酶的活性。
