N Li1, Q Ji, P Hjemdahl. 1. Clinical Pharmacology Unit, Department of Medicine, Karolinska University Hospital (Solna), Stockholm, Sweden. nailin.li@ki.se
Abstract
BACKGROUND: Platelets can bind to, and thereby influence, lymphocyte function. OBJECTIVE: The propensities of different lymphocyte subpopulations to form platelet-lymphocyte conjugates/aggregates (P-Lym) was investigated using four-color whole blood flow cytometry. RESULTS: P-Lym constituted approximately 3% of circulating lymphocytes. Platelet conjugation was most common among large (monocyte-sized) lymphocytes. Platelet activation by ADP slightly increased platelet-T-cell conjugation, mainly to T-cytolytic (Tc) cells, but markedly elevated platelet-natural killer (NK)-cell conjugation. T-cell activation by phytohemagglutinin increased heterotypic conjugation among both T-helper (TH) and Tc cells, whilst NK-cell activation by interleukin-2 affected platelet-NK-cell aggregation little. Neither platelet activation nor lipopolysaccharides-induced B-cell activation enhanced platelet-B-cell aggregation. Activation-dependent heterotypic conjugation was mainly found among large cells, with increased percentages of conjugated cells and more platelets bound per lymphocyte. P-Lym formation initiated by platelet activation was abolished by P-selectin blockade, and tended to be reduced by inhibition of GPIIb/IIIa, CD11b, or CD40L. P-Lym formation initiated by lymphocyte activation was partially inhibited by each of these blocking agents, but more markedly inhibited when the blocking agents were combined. CONCLUSIONS: Platelets selectively bind to larger and activated lymphocytes. T-lymphocyte activation enhances platelet-T-cell aggregation. Platelet activation enhances platelet-Tc aggregation slightly and platelet-NK-cell aggregation markedly, while cellular activation affects platelet-B-cell aggregation little. P-selectin ligation is essential, but GPIIb/IIIa, CD40L, and CD11b also contribute to the heterotypic conjugation.
BACKGROUND: Platelets can bind to, and thereby influence, lymphocyte function. OBJECTIVE: The propensities of different lymphocyte subpopulations to form platelet-lymphocyte conjugates/aggregates (P-Lym) was investigated using four-color whole blood flow cytometry. RESULTS: P-Lym constituted approximately 3% of circulating lymphocytes. Platelet conjugation was most common among large (monocyte-sized) lymphocytes. Platelet activation by ADP slightly increased platelet-T-cell conjugation, mainly to T-cytolytic (Tc) cells, but markedly elevated platelet-natural killer (NK)-cell conjugation. T-cell activation by phytohemagglutinin increased heterotypic conjugation among both T-helper (TH) and Tc cells, whilst NK-cell activation by interleukin-2 affected platelet-NK-cell aggregation little. Neither platelet activation nor lipopolysaccharides-induced B-cell activation enhanced platelet-B-cell aggregation. Activation-dependent heterotypic conjugation was mainly found among large cells, with increased percentages of conjugated cells and more platelets bound per lymphocyte. P-Lym formation initiated by platelet activation was abolished by P-selectin blockade, and tended to be reduced by inhibition of GPIIb/IIIa, CD11b, or CD40L. P-Lym formation initiated by lymphocyte activation was partially inhibited by each of these blocking agents, but more markedly inhibited when the blocking agents were combined. CONCLUSIONS: Platelets selectively bind to larger and activated lymphocytes. T-lymphocyte activation enhances platelet-T-cell aggregation. Platelet activation enhances platelet-Tc aggregation slightly and platelet-NK-cell aggregation markedly, while cellular activation affects platelet-B-cell aggregation little. P-selectin ligation is essential, but GPIIb/IIIa, CD40L, and CD11b also contribute to the heterotypic conjugation.
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