Circulating platelet-neutrophil complexes represent a subpopulation of activated neutrophils primed for adhesion, phagocytosis and intracellular killing

Platelets play a prominent role in linking the processes of inflammation ha emostasis and thrombosis. Recent studies have shown that platelets form het erotypic aggregates with leucocytes via platelet CD62P and leucocyte beta 2 integrins. These interactions have been observed in vitro in blood taken f rom healthy volunteers and in clinical conditions in which thrombosis and i nflammation are prominent. This study investigated the properties of platelet-neutrophil complexes (PN Cs) in anticoagulated whole blood. At rest, neutrophils in PNCs exhibit a s ignificantly more activated adhesion molecule profile than free neutrophils with increased CD11b expression and activation (increased binding of the C D11b/CD18 'activation reporter' monoclonal antibody 24) and decreased CD62L expression. In addition, neutrophils in PNCs phagocytosed significantly mo re Neisseria meningitidis and produced more toxic oxygen metabolites than f ree neutrophils. Stimulation with the platelet agonist adenosine diphosphate (ADP) led to fu rther increases in CD11b expression and activation, loss of CD62L as well a s increased phagocytosis and toxic oxygen metabolite production throughout the whole neutrophil population. When these experiments were repeated with the CD62P blocking antibody G1 the effects were inhibited to a variable ext ent, dependent upon the parameter under investigation. These results indica te that both soluble and contact-dependent factors contribute to platelet-m ediated neutrophil activation. Platelet neutrophil complexes represent a large subpopulation of neutrophil s with a more activated adhesion molecule profile, and a greater capacity f or phagocytosis and toxic oxygen metabolite production. This study provides further support for a role for PNCs in both health and disease.