Localization of the apoptosis-inducing activity of lupus anticoagulant in an annexin V-binding antibody subset.

Abstract

Lupus anticoagulant (LAC) is associated with arterial and venous thrombosis, thrombocytopenia, and recurrent fetal loss. We have reported previously that plasma with LAC activity induces apoptosis in endothelial cells and binds annexin V (Nakamura, N., Y. Shidara, N. Kawaguchi, C. Azuma, N. Mitsuda, S. Onishi, K. Yamaji, and Y. Wada. 1994. Biochem. Biophys. Res. Commun. 205:1488-1493). In this study, we separated two IgG antibody fractions, one with and one without affinity for annexin V, from 10 patients with LAC. LAC and apoptotic activities were localized in the annexin V-binding fraction in all 10 patients. DNA fragmentation was dose-dependent, paralleling the amount of IgG added to the human umbilical vein endothelial cell culture medium, and was inhibited by preincubation with annexin V. Removal of the antiphospholipid antibodies from patient IgG with phospholipid liposomes did not abolish the apoptosis-inducing activities or binding to annexin V. These results imply that patients with LAC often have antibodies that do not bind phospholipids and are responsible for the induction of apoptosis in endothelial cells.

Thrombin-dependent intravascular leukocyte trafficking regulated by fibrin and the platelet receptors GPIb and PAR4

“…While this model is not designed to mimic the precise sequence of pathogenetic events linked to specific thromboinflammatory diseases, it nonetheless provides important insights into the molecular processes by which dying endothelial cells promote leukocyte trafficking in vivo. The disruption of membrane phospholipid asymmetry in endothelial cells leading to PS exposure is a characteristic feature of dying cells regardless of the cause 44,45 , as in the antiphospholipid syndrome 46 , in response to immunomodulatory and chemotherapeutic regimens containing agents such as thalidomide 47 and arsenic 48 , and after ischaemia reperfusion [49][50][51] . Therefore, our observations related to PS-positive endothelial cells after needle injury may have relevance to disease processes.…”

Developmental Profile of Annexin IX and its Possible Role in Programmed Cell Death of the Bombyx mori Anterior Silk Gland

“…2A). ANX proteins are known to be involved in apoptosis in mammals and nematodes (Nakamura et al, 1998;Arur et al, 2003). As 20E triggers PCD of the silk glands, the reciprocal expression of ANX IX and the change in hemolymph ecdysteroid titer suggest a relationship between ANX IX and 20E-induced PCD.…”

Lupus Anticoagulant Induced by the Combination of Valproate and Lamotrigine

“…LAC inhibits coagulation in vitro, but is paradoxically associated with thrombosis in affected patients. Recently it was shown that LAC induces apoptosis in endothelial cells and binds annexin V, a protein that has been suggested to play a role in preventing blood coagulation (9).…”