Bischof P, Haenggeli L, Campana A
Department of Obstetrics and Gynecology, University of Geneva, Switzerland.
Hum Reprod. 1995 Mar;10(3):734-42. doi: 10.1093/oxfordjournals.humrep.a136024.
Collagenolytic activity of cytotrophoblasts is stimulated by glycoproteins of the extracellular matrix and since this stimulation can possibly occur through integrins, we measured the gelatinolytic activity of villous and extravillous cytotrophoblasts according to the type of integrins expressed on these cells. Cytotrophoblasts were isolated from legal abortions, immunopurified with anti-CD45, separated according to their expression of histocompatibility-linked antigen (HLA)-G, alpha 6 or alpha 5 integrin subunits and cultured for 5 days on plastic or agarose. Fetal fibronectin, human chorionic gonadotrophin (HCG) and the gelatinolytic activity were measured in the culture supernatants. Following immunopurification with anti-CD45, the gelatinolytic activity of cytotrophoblasts was significantly higher than before, indicating that contaminating lymphomyeloid cells secreted gelatinolytic inhibitors. HLA-G positive cells secreted significantly more gelatinases than HLA-G negative cells but their HCG secretion was similar. Compared to alpha 5 positive cells, alpha 6 positive cytotrophoblasts secreted significantly more gelatinases, significantly less fibronectin but similar amounts of HCG. We conclude that during trophoblast invasion, extravillous cytotrophoblasts (HLA-G positive) expressing the alpha 6 integrin subunit represent the invasive population of cells (high gelatinase and low fibronectin secretion). When expression of the alpha 5 integrin subunit is turned on, their invasive behaviour ceases and they secrete low amounts of gelatinases and high concentrations of fibronectin.
细胞滋养层细胞的胶原酶活性受到细胞外基质糖蛋白的刺激，由于这种刺激可能通过整合素发生，我们根据这些细胞上表达的整合素类型，测量了绒毛和绒毛外细胞滋养层细胞的明胶酶活性。细胞滋养层细胞从合法流产的样本中分离出来，用抗CD45进行免疫纯化，根据其组织相容性相关抗原（HLA）-G、α6或α5整合素亚基的表达进行分离，并在塑料或琼脂糖上培养5天。在培养上清液中测量胎儿纤连蛋白、人绒毛膜促性腺激素（HCG）和明胶酶活性。用抗CD45进行免疫纯化后，细胞滋养层细胞的明胶酶活性显著高于纯化前，表明污染的淋巴骨髓细胞分泌明胶酶抑制剂。HLA-G阳性细胞分泌的明胶酶明显多于HLA-G阴性细胞，但它们的HCG分泌相似。与α5阳性细胞相比，α6阳性细胞滋养层细胞分泌的明胶酶明显更多，纤连蛋白明显更少，但HCG分泌量相似。我们得出结论，在滋养层细胞侵袭过程中，表达α6整合素亚基的绒毛外细胞滋养层细胞（HLA-G阳性）代表侵袭性细胞群体（高明胶酶分泌和低纤连蛋白分泌）。当α5整合素亚基的表达开启时，它们的侵袭行为停止，分泌少量明胶酶和高浓度纤连蛋白。
