INHIBITION OF FACTOR XA-MEDIATED PROCOAGULANT ACTIVITY OF HUMAN LUNG FIBROBLASTS AND PLEURAL MESOTHELIAL CELLS

Extravascular fibrin deposition characterizes diverse forms of lung an d pleural injury. Fibrin formation in these compartments is locally po tentiated by the assembly and expression of the prothrombinase procoag ulant complex (factors Xa, Va and II) at the surface of human lung fib roblasts and pleural mesothelial cells. We sought to identify structur al domains on factor Xa that mediate expression of prothrombinase acti vity by these cells. In order to accomplish this objective, we used pa nels of monoclonal antibodies (MoAbs) to factor X to block prothrombin ase assembly and function on the surface of cultured human lung fibrob lasts and pleural mesothelial cells. Of 30 factor X MoAbs that recogni zed native factors X and Xa, 10 completely inhibited factor Xa functio n (prothrombin activation), and five others neutralized Xa function wi thout affecting cell-binding, presumably by blocking the prothrombin b inding 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. Ou r results indicate that prothrombinase activity at the surface of lung parachymal or pleural cells can be blocked by MoAbs that interact wit h either the heavy- or light-chain of factors X. Antibodies that neutr alize cell surface-expressed prothrombin activation offer a potential means to arrest pericellular fibrin formation in the lung and pleural space.