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Physiological functions and clinical implications of fibrinogen-like 2:A review

World Journal of Clinical Infectious Diseases 2013年第3期3卷 37-46页

作者： Genyan Yang W Craig Hooper Clinical and Molecular Hemostasis Laboratory Branch Division of Blood Disorders National Center on Birth Defects and Developmental DisabilitiesCenters for Disease Control and Prevention Atlanta GA 30301United States

Fibrinogen-like 2(FGL2) encompasses a transmembrane(m FGL2) and a soluble(s FGL2) form with differential tertiary structure and biological activities. Typically, m FGL2 functions as prothrombinase that is capable of initiating coagulation in tissue without activation of the blood clotting cascade, whereas s FGL2 largely acts as an immunosuppressor that can repress proliferation of alloreactive T lymphocytes and maturation of bone marrow dendritic cells. Protein sequences of FGL2 exhibit evolutionary conservation across wide variety of species, especially at the carboxyl terminus that contains fibrinogen related domain(FRED). The FRED of FGL2 confers specificity and complexity in the action of FGL2, including receptor recognition, calcium affiliation, and substrate binding. Constitutive expression of FGL2 during embryogenesis and in mature tissues suggests FGL2 might be physiologically important. However, excessive induction of FGL2 under certain medical conditions(e.g. pathogen invasion) could trigger complement activation, inflammatory response,cellular apoptosis, and immune dysfunctions. On the other hand, complete absence of FGL2 is also detrimental as lack of FGL2 can cause autoimmune glomerulonephritis and acute cellular rejection of xenografts. All these roles involve m FGL2, s FGL2, or their combination. Although it is not clear how m FGL2 is cleaved off its host cells and secreted into the blood, circulating s FGL2 has been found correlated with disease severity and viral loading among patients with human hepatitis B virus or hepatitis C virus infection. Further studies are warranted to understand how FGL2 expression is regulated under physiological and pathological conditions. Even more interesting is to determine whether m FGL2 can fulfill an immunoregulatory role through its FRED at carboxyl end of the molecule and, and vice versa, whether s FGL2 is procoagulant upon binding to a target cell. Knowledge in this area should shed light on development of s FG

关键词： Fibrinogen-like 2 prothrombinase Immunosuppressor Infectious disease

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