Department of Haematology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa; Tshwane Academic Division of the National Health Laboratory Service, Pretoria, South Africa.
Institute for Cellular and Molecular Medicine, South African Medical Research Council Unit for Stem Cell Research, Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
J Infect. 2017 Jun;74(6):599-608. doi: 10.1016/j.jinf.2017.02.010. Epub 2017 Mar 4.
Platelets orchestrate the inflammatory activities of neutrophils, possibly contributing to pulmonary and myocardial damage during severe pneumococcal infection. This study tested the hypothesis that the pneumococcal toxin, pneumolysin (Ply), activates production of platelet-activating factor (PAF) and thromboxane A (TxA) by neutrophils, these bioactive lipids being potential mediators of neutrophil:platelet (NP) networking.
The effects of recombinant Ply (10-80 ng mL) on the production of PAF and TxA by isolated neutrophils were measured using ELISA procedures, and NP aggregation by flow cytometry.
Exposure of neutrophils to Ply induced production of PAF and, to a lesser extent, TxA, achieving statistical significance at ≥20 ng mL of the toxin. In the case of NP interactions, Ply promoted heterotypic aggregation which was dependent on upregulation of P-selectin (CD62P) and activation of protease-activated receptor 1 (PAR1), attaining statistical significance at ≥10 ng mL of the toxin, but did not involve either PAF or TxA.
Ply induces synthesis of PAF and TxA by human neutrophils, neither of which appears to contribute to the formation of NP heterotypic aggregates in vitro, a process which is seemingly dependent on CD62P and PAR1. These pro-inflammatory activities of Ply may contribute to the pathogenesis of pulmonary and myocardial injury during severe pneumococcal infection.
血小板可调控中性粒细胞的炎症活动，这可能导致严重肺炎球菌感染期间肺部和心肌损伤。本研究旨在验证肺炎球菌毒素肺炎球菌溶血素（Ply）是否能激活中性粒细胞产生血小板激活因子（PAF）和血栓素 A（TxA），这些生物活性脂质可能是中性粒细胞-血小板（NP）网络形成的潜在介质。
采用 ELISA 法检测分离的中性粒细胞中重组 Ply（10-80ng/ml）对 PAF 和 TxA 产生的影响，并采用流式细胞术检测 NP 聚集。
Ply 暴露于中性粒细胞可诱导 PAF 产生，在毒素≥20ng/ml 时达到统计学意义，并且在较小程度上诱导 TxA 产生。在 NP 相互作用的情况下，Ply 促进异质聚集，这依赖于 P-选择素（CD62P）的上调和蛋白酶激活受体 1（PAR1）的激活，在毒素≥10ng/ml 时达到统计学意义，但不涉及 PAF 或 TxA。
Ply 可诱导人中性粒细胞合成 PAF 和 TxA，两者似乎都不参与 NP 异质聚集的形成，这一过程似乎依赖于 CD62P 和 PAR1。Ply 的这些促炎活性可能导致严重肺炎球菌感染期间肺部和心肌损伤的发病机制。
