Soluble fibrin augments spreading of fibroblasts by providing RGD sequences of fibrinogen in soluble fibrin

• Published in: Thrombosis research Vol. 114; no. 4; pp. 293 - 300
• Main Authors: Yang, Wei, Wu, Bin, Asakura, Shinji, Kohno, Isao, Matsuda, Michio
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Ltd 2004; Elsevier Science
• Subjects: Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Cardiology. Vascular system; Cell Adhesion - drug effects; Cell Line; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Disseminated Intravascular Coagulation - blood; Fibrin - isolation & purification; Fibrin - physiology; Fibrinogen - chemistry; Fibrinogen - isolation & purification; Fibroblasts; Fibroblasts - cytology; Fibroblasts - drug effects; Fundamental and applied biological sciences. Psychology; Hormones. Endocrine system; Humans; Medical sciences; Oligopeptides - physiology; Peptide Fragments - chemical synthesis; Peptide Fragments - pharmacology; Pharmacology. Drug treatments; RGD sequences; Solubility; Soluble fibrin; Vertebrates: cardiovascular system; TBS; GPRP; FM; RGD sequences; GRGDSP; Fbg; GRGESP; Soluble fibrin; RGD; mAb; BSA; DMEM; SF; Fibroblasts; Fibrin; Hemostatic; Fibrinogen; Cardiovascular disease; Fibroblast
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2004.06.022

We previously reported that fibroblasts were found to spread far more avidly on NaBr-solubilized fibrin monomer (FM) monolayers than on immobilized fibrinogen (Fbg), indicating that removal of fibrinopeptides by thrombin is a prerequisite for the fibrin-mediated augmentation of cell spreading [J. Biol. Chem. 272 (1997) 8824–8829]. 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 known. Fibroblasts spread on immobilized purified soluble fibrin. Cells spreading on immobilized soluble fibrin were blocked by the exogenous addition of soluble fibrin and glycine–arginine–glycine–aspartic acid–serine–phenylalanine (GRGDSP)-synthetic peptide but not by the addition of fibrinogen or fibrin monomer. However, cell spreading activity was decreased in the surfaces coated with fragment X, whose Aα-chains lack carboxyl-terminal segments including arginine–glycine–aspartic acid (RGD)-2 domain, fibrin monomer complexes. It suggests that the RGD-2 domain of fibrinogen after being complexed with fibrin monomer plays a pivotal role for soluble fibrin-dependent cell spreading. Soluble fibrin in plasma derived from the patients of disseminated intravascular coagulation (DIC) was immuno-purified using the monoclonal antibody (mAb) which specifically recognizes the Ca ++-dependent conformer of fibrinogen. The purified soluble fibrin consisted of desAA-fibrin monomer and two fibrinogen molecules and did show the cell spreading activity. Thus, soluble fibrin in plasma plays a role as the modulator of thrombogenic process in vivo.