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

Abstract

Platelets play a prominent role in linking the processes of inflammation, haemostasis and thrombosis. Recent studies have shown that platelets form heterotypic aggregates with leucocytes via platelet CD62P and leucocyte beta2 integrins. These interactions have been observed in vitro in blood taken from healthy volunteers and in clinical conditions in which thrombosis and inflammation are prominent. This study investigated the properties of platelet-neutrophil complexes (PNCs) in anticoagulated whole blood. At rest, neutrophils in PNCs exhibit a significantly more activated adhesion molecule profile than free neutrophils with increased CD11b expression and activation (increased binding of the CD11b/CD18 'activation reporter' monoclonal antibody 24) and decreased CD62L expression. In addition, neutrophils in PNCs phagocytosed significantly more Neisseria meningitidis and produced more toxic oxygen metabolites than free neutrophils. Stimulation with the platelet agonist adenosine diphosphate (ADP) led to further increases in CD11b expression and activation, loss of CD62L as well as 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 extent, dependent upon the parameter under investigation. These results indicate that both soluble and contact-dependent factors contribute to platelet-mediated neutrophil activation. Platelet neutrophil complexes represent a large subpopulation of neutrophils with a more activated adhesion molecule profile, and a greater capacity for phagocytosis and toxic oxygen metabolite production. This study provides further support for a role for PNCs in both health and disease.

Platelets augment respiratory burst in neutrophils activated by selected species of gram-positive or gram-negative bacteria.

“…The already published data show that neutrophils can affect the adhesion, aggregation and secretion of platelets [14]. The other results show the influence of platelets on chemotaxis, phagocytosis, degranulation and oxygen metabolism of neutrophils [7,15,16]. The key factors engaged in these interactions are lipid mediators as: PAF, LTC4, TXA2, and others [3,6].…”

Clostridium perfringens phospholipase C-induced platelet/leukocyte interactions impede neutrophil diapedesis

“…Neutrophils, however, would retain the ability to bind multiple activated platelets in a rosette pattern. Such interactions are known to hyperstimulate neutrophil respiratory burst activity (Peters et al, 1999;Ruf et al, 1992) and to facilitate chemical cross-talk between these cells, resulting in direct endothelial cell injury and local vascular dysfunction (Ward et al, 1986), and hyperproduction of thromboxanes (Maugeri et al, 1992), leukotrienes (Maugeri et al, 1994) and cytokines (Neumann et al, 1997). Overproduction of these potent immunomodulators could also contribute to local tissue injury and to the systemic manifestations of gas gangrene.…”

Time-dependent platelet-vessel wall interactions induced by intestinal ischemia-reperfusion

“…Interactions between these two cell types can result in a reciprocal activation, resulting in an increased cell adhesion molecule expression, superoxide generation and phagocytic activity of leukocytes (25,28) and increased P-selectin expression by platelets (20). Such cell-cell interactions are likely to increase hours after reperfusion due to the increased expression of transcription-dependent mediators of inflammation.…”