Binding of human factor VII and VIIa to monocytes.

Abstract

A B S T R A C T Human coagulation

Human alveolar macrophages synthesize factor VII in vitro. Possible role in interstitial lung disease.

“…Previous observations in humans indicate that upon appropriate stimulation monocytes initiate coagulation via the extrinsic pathway by expression of tissue factor (7,11,17,36 (Fig. 1).…”

“…These experiments do not, however, determine the source of the Factor VII activity. Alveolar macrophages may be stimulated to express thromboplastin activity and then bind blood-derived Factor VII as reported for human monocytes by Broze (17). We examined the alternative possibility that macrophages may synthesize Factor VII as suggested by Tsao et al (21).…”

“…We estimate the mean Factor VII associated with the cells of sarcoid patients to be 4.7 ng/10' cells (range 0. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] (1,2). Attenuation of the hypercellular characteristics of acute complex glomerulonephritis by antimacrophage antiserum (3) and by defibrinogenation (4) indicated a direct causal role for both the macrophage and fibrin in immunologically mediated tissue injury.…”

A coagulation pathway on bovine aortic segments leading to generation of Factor Xa and thrombin.

“…Thrombin was iodinated by the lactoperoxidase technique (see above); the radiolabeled protein had a specific radioactivity of 4-8 X 103 cpm/ng and the coagulant activity was unaffected by radiolabeling. Factor VII, radioiodinated by the method of Fraker and Speck (28) as modified for Factor VII by Broze (29), had a specific radioactivity of 2-4 X 103 cpm/ng and was homogeneous on SDS-PAGE, migrating as a single band of radioactivity at a molecular weight of 54,000.…”

Factor VIIa Interaction With Tissue Factor and Endothelial Cell Protein C Receptor on Cell Surfaces

“…This suggests that EPCR acts as a true receptor for FVIIa. However, in comparison with FVIIa affinity for cell-associated TF (Kd of approximately 100 pM-3 nM) (10,11,33), the affinity of FVIIa for EPCR on endothelium is relatively weak (Kd of approximately 40-50 nM). Nonetheless, as protein C also binds to EPCR with a similar affinity, even at plasma concentrations of 70 nM (34), FVIIa will still be able to bind to EPCR.…”