Macrophages Synthesize Factor X and Secrete Factor X/Xa-containing Prothrombinase Activity into the Surrounding Medium

Abstract

SummaryActivation of the coagulation cascade, mediated by various monocyte/macrophage procoagulants, is an important component in the pathology of inflammatory disease. The type of procoagulant expressed may vary between different monocyte/macrophage subtypes and may differ depending on how the cells are treated. In the present study we show that both murine peritoneal macrophages and human adherent synovial cells from rheumatoid arthritis lesions express prothrombinase activity that was inhibited by anti-Factor X antibodies. Northern blot analysis showed that Factor X was transcribed by the murine peritoneal cells and Western blot analysis showed the presence of Factor X antigen. Further experiments showed that the prothrombinase activity was secreted by the cells into the medium in a detergent-sensitive form, suggesting that the prothrombinase is released on small lipid-containing vesicles.

Expression of factor V by resident macrophages boosts host defense in the peritoneal cavity

“…Work beginning in the 1980s revealed that LPMs produce FV in culture (Osterud et al, 1981), including production of a functional prothrombinase complex (activated FV/activated FX; Pejler et al, 2000) long before it was recognized that F5 mRNA expression was selective to LPMs. Although the liver is a known source of FV, expression of FV by LPMs led us to hypothesize these macrophages maintain FV levels in peritoneal fluid in the steady state.…”

Lysyl oxidase-like 2 processing by factor Xa modulates its activity and substrate preference

“…FXa promotes the proliferation and migration of SMCs and enhances the secretion of fibronectin, collagen, and TGF-β in fibroblasts [48][49][50][51] . FXa mediates intracellular signaling in many cell types, including macrophages, endothelial cells, fibroblasts, vascular smooth muscle cells, and cancer cells [50][51][52][53][54][55][56] . The effect of FXa signaling is highly specific according to the tissue and cell type.…”

Mitochondrial ferritin expression in human macrophages is facilitated by thrombin‐mediated cleavage under hypoxia

“…Although we could not determine whether thrombin was localized inside macrophages or remained at the cell membrane, it is conceivable that processes like micro‐ or macropinocytosis may promote uptake of prothrombin. However, it is known that macrophages synthesize factor X and release factor X/Xa‐containing prothrombinase activity into its microenvironment [33]. Thrombin promotes an inflammatory macrophage phenotype and thus sensitizes cells towards inflammatory stimuli [34].…”