Platelet-leukocyte-cross-talk in diabetes mellitus.
The physiological meaning of platelets has been best documented for acute coronary syndromes where platelets act as "first responsive elements" triggering the final occlusive thrombus after plaque rupture has occurred. This situation is particularly relevant for patients with NIDDM-type diabetes regularly showing complicated plaque architecture. Predictive power for acute ischemic events e.g. following angioplasty has been proven, and this has dominated the attention exclusively towards the hemostatic function of platelets. Meanwhile, a variety of particularly important platelet features have been identified: a) promotion of liquid phase coagulation; b) regulation of the local vascular tone; c) active modulation of tissue modeling at lesion sites; d) adhesion molecule-mediated communication with a variety of corpuscular blood (and non-blood cells). With emerging recognition of the latter role, the pathophysiological scope of platelets exceeds the well-established role as microemboli, local atherosclerosis amplifiers and triggers of gross thrombosis. In diabetes mellitus of either type, increased populations of circulating platelets have been identified expressing activation dependent adhesion molecules such as activated alpha 2 beta 3 (GPIIbIIIa), lysosomal GP53, thrombospondin or, perhaps most importantly "P-selectin" (CD62 p). This suggests that these adhesion molecules among others can also mediate platelet-leukocyte interactions potentially resulting in inflammatory tissue damaging processes in addition to the immanent tendency towards (micro-)thrombosis. This review works out a more general view on the meaning of platelet activation beyond hemostaseology and updates the actual knowledge of platelet-leukocyte communication checkpoints with particular reference to the diabetic state outlining new pharmacological concepts for intervention.
Tschoepe
D
D
Diabetes Research Institute, Heinrich Heine University of Duesseldorf, Germany.
Rauch
U
U
Schwippert
B
B
D001792:Blood Platelets / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology*; D002450:Cell Communication; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D006801:Humans; D007962:Leukocytes / Q000502:physiology*; D015539:Platelet Activation
D015815:Cell Adhesion Molecules