Agonistic anti-ICAM-1 antibodies in scleroderma: activation of endothelial pro-inflammatory cascades.

Background: Scleroderma (SSc) is a complex autoimmune disorder that can be characterised by the presence 2of circulating autoantibodies to nuclear, cytoplasmic and cell surface antigens. In particular antibodies directed against endothelial cell antigens (anti-endothelial cell antibodies; AECA) have been detected. ICAM-1 is an adhesion molecule expressed on the surface of human endothelial cells.

Microparticle formation after exposure of blood to activated endothelium under flow.

Increased numbers of circulating microparticles (MPs) are indicative of poor clinical outcome in a number of inflammatory disorders, including atherosclerosis. Platelets and megakaryocytes are a major source of MP and are identified by presence of CD42b on the MP surface. MP shed from activated platelets can be identified by presence of P-selectin (CD62P).

Expression of blood coagulation factors on monocytes after exposure to TNF-treated endothelium in a novel whole blood model of arterial flow.

Activated blood monocytes are a major source of tissue factor (TF), the principal initiator of blood coagulation. TF can be shed from the monocyte surface in association with microparticles (MPs) and increased numbers of circulating MPs are indicative of poor clinical outcome in a number of inflammatory disorders, including atherosclerosis. The mechanisms coupling inflammation with aberrant TF production/activity remain obscure but the protease-activated receptor (PAR) family has been implicated.