Cross-talking between lymphocytes and platelets and its regulation by nitric oxide and peroxynitrite in physiological condition and endotoxemia

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Abstract

Aims:

Cross-talk between platelets and lymphocytes may play a role in different pathological conditions like sepsis. This study aimed to investigate the effect of lymphocytes on platelet aggregation in lipopolysaccharide (LPS)-stimulated and non-stimulated cells.

Main methods:

Lymphocytes and platelet-rich plasma (PRP) were obtained from rat arterial blood. Platelets (1.2 × 108 platelets/ml) were incubated with lymphocytes (0.8 × 106 cells/ml) in the presence or not of LPS (100 μg/ml), after which ADP (5 μM)-induced platelet aggregation was carried out.

Key findings:

Lymphocytes inhibited by 51% the platelet aggregation, which was significantly prevented by the non-selective NO inhibitor l-NAME (300 μM) or the selective iNOS inhibitor 1400 W (100 μM), as well as by the soluble guanylyl cyclase (sGC) inhibitor ODQ (10 μM). The platelet inhibition by lymphocytes was accompanied by 2-fold increase of intraplatelet cGMP levels. Next, lymphocytes and platelets were co-incubated with LPS for 6 h. In LPS-treated cells, lymphocytes produced a larger inhibition of platelet aggregation (62%), despite the same elevation of cGMP levels (2.2-fold increase). This inhibitory effect was prevented by l-NAME and 1400 W, but rather unaffected by ODQ. The peroxynitrite (ONOO−) scavenger −(−)epigallocatechin gallate (ECG, 100 μM) abolished the inhibition by lymphocytes on platelet aggregation in LPS-treated cells, but not in non-treated cells.

Significance:

Our results show that lymphocytes act to inhibit platelet aggregation via iNOS-derived NO release and cGMP generation. In presence of LPS, ONOO− production accounts for the platelet inhibition.

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