Coulot P, Bouchara J P, Renier G, Annaix V, Planchenault C, Tronchin G, Chabasse D
Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Universitaire, Angers, France.
Infect Immun. 1994 Jun;62(6):2169-77. doi: 10.1128/iai.62.6.2169-2177.1994.
Interaction between Aspergillus fumigatus conidia and different proteins known to mediate the attachment of malignant tumor cells or microorganisms to the host tissues was studied in vitro. Flow cytometry using fluorescein isothiocyanate-conjugated fibrinogen confirmed that binding of human fibrinogen to the conidia was dose dependent and specific. Binding was inhibited by unlabeled fibrinogen and by basement membrane laminin. Moreover, the expression of fibrinogen receptors at the surfaces of conidia seemed to be related to the maturation of the conidia. Binding sites appeared to be located in the D domains of the fibrinogen molecule. However, the peptide sequence recognized by the fungus could not be identified but was different from the classical adhesive recognition sequences, RGDS and fibrinogen gamma-chain dodecapeptide. In addition, an assay of adherence to proteins immobilized onto microtiter plates allowed us to establish the role of these interactions in fungal adhesion. Conidia strongly adhered to human fibrinogen and to laminin but not to fibronectin. Adhesion to fibrinogen substrates was specific, since it was inhibited by soluble fibrinogen and by specific antibodies, and seemed to be mediated by the D domains of the molecule. Study of the adhesion of numerous strains or clinical isolates to various mammalian fibrinogens did not reveal any particular affinity of strains for some animal species. Finally, by cultivation of the fungus in the presence of 125I-human fibrinogen and analysis of the radiolabeled material bound to the surface of the fungus, we were able to specify the sequence of events allowing its installation within the host. The interactions identified here may play an important role in governing fungal adherence and host tissue invasion.
体外研究了烟曲霉分生孢子与已知介导恶性肿瘤细胞或微生物附着于宿主组织的不同蛋白质之间的相互作用。使用异硫氰酸荧光素偶联的纤维蛋白原进行的流式细胞术证实，人纤维蛋白原与分生孢子的结合呈剂量依赖性且具有特异性。未标记的纤维蛋白原和基底膜层粘连蛋白可抑制这种结合。此外，分生孢子表面纤维蛋白原受体的表达似乎与分生孢子的成熟有关。结合位点似乎位于纤维蛋白原分子的D结构域。然而，真菌识别的肽序列无法确定，但与经典的粘附识别序列RGDS和纤维蛋白原γ链十二肽不同。此外，对固定在微量滴定板上的蛋白质的粘附试验使我们能够确定这些相互作用在真菌粘附中的作用。分生孢子强烈粘附于人纤维蛋白原和层粘连蛋白，但不粘附于纤连蛋白。对纤维蛋白原底物的粘附具有特异性，因为它受到可溶性纤维蛋白原和特异性抗体的抑制，并且似乎由分子的D结构域介导。对多种菌株或临床分离株与各种哺乳动物纤维蛋白原粘附的研究未发现菌株对某些动物物种有任何特殊亲和力。最后，通过在125I-人纤维蛋白原存在下培养真菌并分析与真菌表面结合的放射性标记物质，我们能够确定其在宿主体内定植的事件顺序。这里确定的相互作用可能在控制真菌粘附和宿主组织侵袭中起重要作用。
