1044 Monocyte Factor

The monocyte has been perceived as a relatively inactive member of the monocyte /macrophage series, i.e., a cell in transport to an anatomic site where differentiation to the macrophage will occur. Modification of this perception is meri ted in light of the ready capacity of monocytes, as well as their tissuelocalized progeny, the elicited macrophage, to initiate and propagate coagulation protease pathways (reviewed in references 1-4). The human monocyte given appropriate direct collaboration by bacterial lipopolysaccharide (LPS), 1 immune complex-st imulated T lymphocytes (5-7), or a lymphokine (8, 9) from allogeneicaily or antigen-stimulated T cells (10, 1 1), produces and expresses on its surface a cell membrane lipoprotein, i.e., tissue factor, the initiating cofactor of the extrinsic coagulation protease pathway (12, 13). This initiating event is attributable to the calcium-dependent binding of Factor VII or VIIa to tissue factor (14, 15) to form a molecular complex capable of efficiently converting the zymogen Factor X to its active form by virtue of the limited proteolytic specificity of Factor VII and VIIa. This protease, the only coagulation protease that is proven to be active in the zymogen form (16), also can proteolytically activate Factor IX, of the intrinsic pathway (17). In the human (18) and the mouse (19) an independent procoagulant protease, monocyte prothrombinase, has been identified. This protease can directly mediate the conversion of prothrombin to thrombin. Other studies have implicated additional cellular proteases including a rabbit tumor cell-associated Factor X activating cysteine protease (20), a Factor X-activating protease in LPS-stimulated rabbit Kuppfer cells (21), a vitamin K-dependen t protease activity associated with Lewis lung carcinoma (22), and a murine macrophage protease with Factor X-activating properties (23), We have implicated the synthesis of valid This is publication number 3210-IMM. This study was supported by Grants CA-28166 and HL28672 from the National Institutes of Health. Dr. Tsao was a fellow of the California Heart Association. Dr. Curtiss is an Established Investigator of the American Heart Association. Dr. Betty Tsao's current address is: Department of Medicine, Indiana University School of Medicine, 541 Clinical Drive, Long-Clinical 492, Indianapolis, IN 46223. z Abbreviations used in this paper: EDTA, ethylene diaminetetracetic acid; Mo, monocytes; LPS, bacterial lipopolysaccharide; PBM, peripheral blood mononuclear cells; PCA, procoagulant activity; Ti,a, inducer T cells.