Complete downmodulation of P-selectin glycoprotein ligand in monocytes undergoing apoptosis.

Objective: Apoptotic monocytes release membrane microparticles which may play a major role in thrombogenicity through a P-selectin glycoprotein ligand (PGSL-1)-mediated mechanism. We have studied systematically the regulation of PSGL-1 expression and function in apoptotic monocytic cells.

Methods And Results: PSGL-1 expression (flow cytometry, immunofluorescence microscopy, immunoblot) was virtually abolished in apoptotic monocytes by proteolytic shedding.

Membrane environment rather than tissue factor expression determines thrombin formation triggered by monocytic cells undergoing apoptosis.

Monocyte apoptosis is an important determinant of atherothrombosis. Two major mechanisms for apoptosis-associated thrombogenicity have been described: exposure of negatively charged membrane phospholipids and up-regulation of tissue factor (TF). However, the relative importance of these mechanisms is unclear.

Rapid release of active tissue factor from human arterial smooth muscle cells under flow conditions.

Circulating tissue factor (TF) is an important determinant of coronary thrombosis. Among other cell types, such as monocytes, vascular smooth muscle cells (SMCs) are capable of releasing TF. When studied under static conditions, SMCs do release TF, but this process is slow and, thus, cannot explain the elevated levels of circulating TF, as observed in patients with acute coronary syndromes.