Si Tahar M, Renesto P, Balloy V, Chignard M
Unité de Pharmacologie Cellulaire, Institut Pasteur, Paris, France.
Eur Cytokine Netw. 1994 Sep-Oct;5(5):455-60.
We previously showed that two polymorphonuclear neutrophil (PMN)-derived proteinases, namely cathepsin G (Cat. G) and elastase (HLE), acting in synergy activated nearby platelets in vitro. This cellular interaction could result in a pathology such as the adult respiratory distress syndrome (ARDS). Since elevated levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) were detected in these patients and therefore could be involved in this disease, we looked for their effects in the PMN-platelet cooperation system. Addition of IL-8 to mixed suspensions of PMN and platelets induced weak but significant platelet aggregations. Upon preincubation with TNF-alpha, aggregations triggered by IL-8 were significantly increased. The targets of these cytokines were not the platelets but the PMNs. This was shown by following beta-glucuronidase release and more interestingly by measuring the enzymatic activities of Cat. G and HLE in the supernatant. Inhibition of the platelet response upon addition of a serine proteinase inhibitor, eglin C, clearly demonstrated the involvement of these two enzymes. Taken together, these results constitute an additional argument for the role of the PMN-platelet interaction in ARDS.
我们先前表明，两种多形核中性粒细胞（PMN）衍生的蛋白酶，即组织蛋白酶G（Cat. G）和弹性蛋白酶（HLE），协同作用可在体外激活附近的血小板。这种细胞间相互作用可能导致诸如成人呼吸窘迫综合征（ARDS）之类的病理状况。由于在这些患者中检测到肿瘤坏死因子-α（TNF-α）和白细胞介素-8（IL-8）水平升高，因此它们可能与该疾病有关，我们研究了它们在PMN-血小板合作系统中的作用。将IL-8添加到PMN和血小板的混合悬浮液中会诱导微弱但显著的血小板聚集。在用TNF-α预孵育后，由IL-8触发的聚集显著增加。这些细胞因子的作用靶点不是血小板，而是PMN。这通过跟踪β-葡萄糖醛酸酶的释放得以证明，更有趣的是通过测量上清液中Cat. G和HLE的酶活性得以证明。添加丝氨酸蛋白酶抑制剂依林C后对血小板反应的抑制清楚地表明了这两种酶的参与。综上所述，这些结果为PMN-血小板相互作用在ARDS中的作用提供了额外的证据。
