Major basic protein binding to thrombomodulin potentially contributes to the thrombosis in patients with eosinophilia

Abstract

The contribution of an eosinophil granule protein, major basic protein (MBP), to the pathogenesis of thrombosis seen in patients with eosinophilia was investigated. The sera from eosinophilic patients containing elevated levels of MBP inhibited thrombomodulin (TM) function as a cofactor for the thrombin-catalysed activation of protein C more significantly than those from normal individuals (means 48.5% v 17.4%, respectively). It was suggested that the binding of mature MBP in the sera to TM was electrostatic, because mature MBP (pI 10.9) bound to TM, whereas pro-MBP (pI 6.2) did not. The inhibition of TM cofactor activity by eosinophil granule proteins was mainly attributed to the mature MBP, because MBP-depleted eosinophil granule proteins did not inhibit TM cofactor activity significantly. This inhibition seemed to be due to the specific thrombin-binding to TM being blocked. We concluded that eosinophil granule proteins, particularly MBP, potentially contribute to the hypercoagulation seen in some conditions of eosinophilia, at least because of the inhibition of TM function as a cofactor of the anticoagulation system.

Eosinophil count is positively correlated with coronary artery calcification

“…In addition, major basic protein or eosinophil cationic protein, which is an eosinophil granule protein, activates platelets and promotes thrombus formation by inhibiting the function of thrombomodulin in hypereosinophic syndrome or allergic disease. 16,17 Rohrbach et al 18 reported that major basic protein and eosinophilic peroxidase activate platelets. Emanuele et al 19 suggested that increased eotaxin levels, an eosinophil-specific chemoattractant, are associated with the presence of coronary artery disease and that circulating levels of this chemokine may reflect the extent of coronary atherosclerosis.…”

Eosinophilic biomarkers for detection of acute exacerbation of chronic obstructive pulmonary disease with or without pulmonary embolism

“…Case reports have stated that eosinophilia in patients may be accompanied by thromboembolisms (40)(41)(42). The secretion of ECP (21,43), EDN (43) and MBP (43,44) has been implicated in increasing the probability of thrombosis formation. MBP also inhibits the binding of thrombomodulin to thrombin and activates protein C, leading to decreased coagulation factor V degradation (44).…”

Eosinophilic Vasculitis: Time for Recognition of a New Entity?

“…Eosinophilic Cationic Protein (ECP) has been implicated in thrombogenesis by enhancing factor XII activity and binding endogenous heparanoids [6,7]. Another granule content, Major Basic Protein (MBP) may also damage endothelium directly and thereby expose collagen leading to thrombosis [8,9]. Although widespread vasculitis and micorthrombosis results in the characteristic multiple organ dysfunction typical of the vasculitides, some cases may present only with thrombotic complications involving larger vessels.…”