Platelets stimulated by IgG-coated surfaces bind and activate neutrophils through a selectin-dependent pathway

Abstract

Blood platelets bind rapidly to foreign surfaces and interact with adsorbed proteins and neutrophil granulocytes. We demonstrate by use of luminol-amplified chemiluminescence under stirred and nonstirred conditions that platelets at IgG-coated surfaces amplify the neutrophil extracellular release of reactive oxygen species (ROS). The neutrophil response involved tyrosine phosphorylation, but was only in part induced by neutrophil F c -receptor stimulation. The platelet mediated effects were contact-dependent since the respiratory burst was inhibited when the IgG-stimulated platelets were removed by filtration, but not when they were fixed in paraformaldehyde. Bodipyphallacidin-staining of filamentous actin (F-actin) revealed that an actin-dependent platelet adhesion supported the subsequent adhesion and spreading of neutrophils. The neutrophil ROS-response was lowered when the interaction between platelet P-selectin (CD62P) and neutrophil P-selectin glycoprotein ligand-l (PSGL-1 or CD162) was inhibited. The blocking of L-selectin (CD62L) or blocking of the interaction between platelet glycoprotein (Gp) IIb/IIIa and neutrophil complement receptor 3 (CR3) showed no effect. We conclude that platelet activation on immobilized IgG trigger a contact-dependent "frustrated" phagocytosis by neutrophils, associated with a release of toxic ROS. IgG-stimulated platelets activate neutrophils -Wetterö et al.3

Effects of platelet release products on neutrophilic activity in human whole blood

“…Platelets appear to affect neutrophil function in a contactindependent manner [3]. Depending on the type of stimulus and experimental conditions, platelets have shown to either inhibit or stimulate neutrophillc functions [18,19]. Stimulated platelets release many low-molecular weight substances, such as ATP, ADP, GTP, GDP, 5HT, and calcium ions from their dense bodies [6,20] and also high-molecular weight substances such as platelet-derived growth factor, fibronectin, and b-TG from their agranules [6], and MAPPs [9 -14].…”

De-Activation of Neutrophils in Suspension by Fluid Shear Stress: A Requirement for Erythrocytes

“…Activation and increased superoxide production are also observed in suspended neutrophils passing through a flow chamber whose surface is coated by activated platelets, and suppressed by a PSGL-1 blocker, but not by L-selectin blockers. 37 Co-existence of the activated platelets also increases chemotactic migration and cytosolic f-actin of neutrophils. 2 Superoxide production or NADPH/xanthine oxidase activity in adherent neutrophils is potentially regulated via a tyrosin phosphorylation pathway.…”

C1q induces a rapid up-regulation of P-selectin and modulates collagen- and collagen-related peptide-triggered activation in human platelets

“…We and others have reported that P-selectin binding to its ligand PSGL-1 is crucial in the formation of platelet-neutrophil aggregates (May et al, 2007;Wetterö et al, 2003), which are formed during different inflammatory conditions e.g. cardiovascular disease.…”

“…Upon platelet activation, P-selectin (CD62P) is translocated from the α-granules to the platelet surface. This up-regulation of P-selectin is proven to play an important role in the aggregate formation between platelets and PSGL-1 (CD162) bearing cells, such as neutrophil granulocytes (May et al, 2007;Wetterö et al, 2003). …”

“…Since P-selectin plays an important role in the adhesion between platelets and neutrophils (May et al, 2007;Wetterö et al, 2003), we investigated whether the observed C1q-mediated down-regulation of P-selectin in collagen-stimulated platelets affected the formation of platelet-neutrophil aggregates. When a mixture of platelets and neutrophils were challenged with collagen (3 μg/mL) the formation of platelet-platelet aggregates as well as plateletneutrophil aggregates was markedly increased compared to the unstimulated control (Fig.…”