Conversion of platelets from a proaggregatory to a proinflammatory adhesive phenotype: role of PAF in spatially regulating neutrophil adhesion and spreading.
The ability of platelets to provide a highly reactive surface for the recruitment of other platelets and leukocytes to sites of vascular injury is critical for hemostasis, atherothrombosis, and a variety of inflammatory diseases. The mechanisms coordinating platelet-platelet and platelet-leukocyte interactions have been well defined and, in general, it is assumed that increased platelet activation correlates with enhanced reactivity toward other platelets and neutrophils. In the current study, we demonstrate a differential role for platelets in supporting platelet and neutrophil adhesive interactions under flow. We demonstrate that the conversion of spread platelets to microvesiculated procoagulant (annexin A5-positive [annexin A5+ve]) forms reduces platelet-platelet adhesion and leads to a paradoxical increase in neutrophil-platelet interaction. This enhancement in neutrophil adhesion and spreading is partially mediated by the proinflammatory lipid, platelet-activating factor (PAF). PAF production, unlike other neutrophil chemokines (IL-8, GRO-alpha, NAP-2, IL-1beta) is specifically and markedly up-regulated in annexin A5+ve cells. Physiologically, this spatially controlled production of PAF plays an important role in localizing neutrophils on the surface of thrombi. These studies define for the first time a specific proinflammatory function for annexin A5+ve platelets. Moreover, they demonstrate an important role for platelet-derived PAF in spatially regulating neutrophil adhesion under flow.
Kulkarni
Suhasini
S
Australian Centre for Blood Diseases, Monash University and Baker Heart Research Institute, at Alfred Medical Research and Education Precinct, Prahran, Victoria, Australia.
Woollard
Kevin J
KJ
Thomas
Stephen
S
Oxley
David
D
Jackson
Shaun P
SP
D017304:Annexin A5 / Q000378:metabolism; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology*; D010972:Platelet Activating Factor / Q000502:physiology*; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D013927:Thrombosis / Q000378:metabolism / Q000473:pathology
D017304:Annexin A5; D053583:Interleukin-1beta; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; C028254:von Willebrand factor receptor; D003094:Collagen; D002118:Calcium