Beta-2-glycoprotein I expression on monocytes is increased in anti-phospholipid antibody syndrome and correlates with tissue factor expression

Abstract

SUMMARYIt is well known that monocytes may play an active role in thrombogenesis, since they may express on their surface tissue factor, the major initiator of the clotting cascade. The results of this investigation demonstrate beta-2-glycoprotein I ( b 2 -GPI) mRNA expression by human peripheral blood monocytes, indicating that these cells synthesize b 2 -GPI. In addition, we show b 2 -GPI expression on cell surface of these cells by flow cytometric analysis, and the presence of this protein in cell lysate by Western blot. Interestingly, b 2 -GPI expression on monocytes is significantly increased in patients with antiphospholipid syndrome (APS) or systemic lupus erythematosus (SLE) as against healthy blood donors and correlates with tissue factor expression on monocytes. These findings support the view that monocytes are able to synthesize b 2 -GPI and suggest that patients with APS may have increased b 2 -GPI exposure on cell surface, which leads to persistently high monocyte tissue factor expression and consequently to a prothrombotic diathesis.

RT-PCR and in situ hybridization analysis of apolipoprotein H expression in rat normal tissues

“…More recently apoH mRNA was found by RT-PCR on RNA extracted from other tissues (intestine, placenta, foetal astrocytes, lymphocytes) or cultured cells (transformed cell lines) such as choriocarcinoma, hepatoma (36), colon adenocarcinoma (35), neuroblastoma, umbilical vein endothelial cells (HUVEC, but not for Alvarado-de la Barrera, 39), astrocytoma, glioblastoma cells (40) and in monocytes (41).…”

Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target

“…The best described antigen in APS is β-2 glycoprotein I (β 2 GPI). β 2 GPI, a cationic lipid-binding protein with unclear function, is made especially by the liver and circulates at high levels in plasma (50-200 μg/ml) (6,7). It has been suggested that anti-β 2 GPI antibodies potentiate thrombosis by engaging β 2 GPI on cell surfaces, thereby promoting cell activation (8)(9)(10).…”

The role of TLR2 in the inflammatory activation of mouse fibroblasts by human antiphospholipid antibodies

“…[4][5][6][7][8] Furthermore, APLAs activate monocytes and platelets, the latter in the presence of subactivating doses of thrombin. [9][10][11][12] The activation of these cells leads to inflammatory and procoagulant responses that may underlie the hypercoagulable state that characterizes APS. 13,14 The mechanisms of cell activation by APLAs are still incompletely understood.…”