Platelet-Neutrophil Interactions in Uremic Patients: Effects on Neutrophil Superoxide Anion Production and Chemiluminescence

Abstract

Isolated resting platelets are able to limit neutrophil activation and then can control the tissue-damaging potential of activated neutrophils. In the present study, platelet-neutrophil interactions have been evaluated in 10 uremic patients; the blood samples have been collected before the hemodialysis session. Twelve normal subjects served as controls. Platelets and neutrophils have been isolated and recombined in an autologous ex vivo system. Anion superoxide production and chemiluminescence (which is related to hypochlorous acid production) have been evaluated after stimulation with N-formyl-methionyl-leucyl-phenylalanine. Coincubation of platelets from normal subjects with autologous neutrophils led to a dose-dependent inhibition of both superoxide anion generation induced by N-formyl-methionyl-leucyl-phenylalanine and chemiluminescence. Instead, platelets from uremic patients have not affected superoxide anion production by autologous neutrophils. The chemiluminescence was reduced by coincubation with autologous platelets only at the highest platelet-neutrophil ratio (100:1). In conclusion, the modulation exerted by platelets towards neutrophil activation can be impaired in chronic uremia. Therefore, the tissue-damaging potential of circulating neutrophils, due to toxicity by superoxide anion and hypochlorous acid, may be increased.

Neutrophil Reactive Oxygen Species Production during Hemodialysis: Role of Activated Platelet Adhesion to Neutrophils through P-Selectin

“…The results of the present study suggest that a dynamic interplay between platelets and neutrophils may be of rel evance to uremic patients, as recently reported [25], Mechanisms involving different adhesion molecules, whether singly or in concert, can mediate the intercellular contacts between platelets and neutrophils during dialy sis. Interactions between P-selectin (GMP-140/PAD-GEM/CD62P) expressed on platelets and the sialylLewis* molecule (CD 15s) present on the neutrophil sur face mediate the adhesion of activated platelets to neutro phils [2,3,[26][27][28], and this mechanism of heterotypic cell-cell interaction might be at work during hemodialysis [8], Platelet-neutrophil coaggregate formation could also be mediated by the platelet membrane glycoprotein com plex GPIIb-IIIa [29].…”

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

“…The interaction between phagocytic cells and bacteria induces activation of membrane oxidase which in turn triggers a metabolic response as respiratory burst in phagocyte. A number of ROS such as singlet oxygen, hydroxyl radical, superoxide anion are formed during that process [8]. In the presence of luminol, ROS cause the emission of light [9].…”

An Apolipoprotein CIII-Derived Peptide, Hatktak, Activates Macromolecular Activators of Phagocytosis from Platelets (MAPPs)

“…When thrombi are formed, activated platelets release a lot of substances while adhering to subendothelial connective tissues, recruiting other platelets and aggregating together. In these regions with thrombus formation or platelet activation, it is possible that platelets affect leukocytic function via the action of the released products, since the substances released from platelets include factors that activate [1][2][3][4][5][6][7][8][9][10][11][12][13][14] and suppress [15][16][17][18][19][20][21][22] neutrophilic functions.…”