可溶性血纤蛋白促进细胞伸展及其作用机制

Cell Spreading Promoted by Soluble Fibrin and its Mechanism

可溶性血纤蛋白（ｓｏｌｕｂｌｅｆｉｂｒｉｎ，ＳＦ）为血纤蛋白单体和血纤蛋白原１∶２的复合物．现已知在血液凝固系统被激活的病理状态下，存在于循环血液中，然而它的生理作用仍然不明．首次发现细胞能在固定的ＳＦ上伸展，并能被外源性ＳＦ及精氨酸－甘氨酸－天冬氨酸（ＲＧＤ）合成肽所抑制，但不能被血纤蛋白原和血纤蛋白单体所抑制，提示ＳＦ形成后其结构变化是引起细胞伸展的关键．片段Ｘ（缺乏ＲＧＤ２序列的血纤蛋白原片段）与血纤蛋白单体形成的复合物，使细胞伸展活性明显减低，提示在ＳＦ结构中，血纤蛋白原的ＲＧＤ２序列在细胞伸展中起重要作用．同时发现ＤＩＣ患者血浆中的ＳＦ也具有细胞伸展活性．

Soluble fibrin (SF),a 1∶2 complex of fibrin monomer and fibrinogen,is known to be present in the circulating blood under the pathological condition in which blood coagulation is activated.However,its physiological roles are still incompletely understood.It is for the first time that SF was observed for a new aspect which augments spreading of fibroblasts by function as an adhesion molecule.SF fractions were purified by using a Gel filtration column (Sephacryl S 300) and evaluated for their cell spreading activity.Human fibroblasts spread on SF,and cell spreading was blocked by the exogenous addition of SF and GRGDSP synthetic peptide,but not by the addition of fibrinogen or fibrin monomer.The results thus indicated that a special conformation elicited in the SF might be responsible for supporting the cell adhesion.Cell spreading activity was decreased on the surfaces coated with fragment X whose Aα chains lacking carboxyl terminal segments including RGD 2 domains,and fibrin monomer complexes.It was suggested that RGD 2 domain of fibrinogen after complexed with fibrin monomer played a pivotal role for SF dependent cell spreading.SF in the plasma derived from the patient with disseminated intravascular coagulation syndrome (DIC) was immuno purified using the monoclonal antibody which specifically recognized Ca 2+ dependent conformer of fibrinogen.The purified SF consisted of desAA fibrin monomer and two fibrinogen molecules and did show the cell spreading activity. Thus SF in plasma played an important role for the modulator of thrombogenic process in vivo.