Inhibition of factor Xa-mediated procoagulant activity of human lung fibroblasts and pleural mesothelial cells
| Autor: | Steven Idell, Anuradha Kumar, Daryl S. Fair, Kathy Koenig, Alice R. Johnson |
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| Rok vydání: | 1995 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.drug_class Biology Monoclonal antibody Fibrin Mice chemistry.chemical_compound Prothrombinase medicine Animals Humans Fibroblast Lung Cells Cultured Mice Inbred BALB C Factor X Antibodies Monoclonal Factor V Fibroblasts respiratory system Molecular biology Blood Coagulation Factors medicine.anatomical_structure Coagulation chemistry Cell culture Factor Xa Immunology biology.protein Pleura Female Prothrombin Antibody Protein Binding |
| Zdroj: | European Respiratory Journal. 8:2038-2045 |
| ISSN: | 1399-3003 0903-1936 |
| Popis: | Extravascular fibrin deposition characterizes diverse forms of lung and pleural injury. Fibrin formation in these compartments is locally potentiated by the assembly and expression of the prothrombinase procoagulant complex (factors Xa, Va and II) at the surface of human lung fibroblasts and pleural mesothelial cells. We sought to identify structural domains on factor Xa that mediate expression of prothrombinase activity by these cells. In order to accomplish this objective, we used panels of monoclonal antibodies (MoAbs) to factor X to block prothrombinase assembly and function on the surface of cultured human lung fibroblasts and pleural mesothelial cells. Of 30 factor X MoAbs that recognized native factors X and Xa, 10 completely inhibited factor Xa function (prothrombin activation), and five others neutralized Xa function without affecting cell-binding, presumably by blocking the prothrombin binding site. Western blots showed that these inhibitory MoAbs reacted with the Xa heavy-chain. One MoAb that recognized the factor Xa light-chain blocked prothrombin activation at the factor Va binding site. Our results indicate that prothrombinase activity at the surface of lung parachymal or pleural cells can be blocked by MoAbs that interact with either the heavy- or light-chain of factors X. Antibodies that neutralize cell surface-expressed prothrombin activation offer a potential means to arrest pericellular fibrin formation in the lung and pleural space. |
| Databáze: | OpenAIRE |
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