Chumpitazi B F, Simon J, Polack B, Peyron F, Picot S, Ricard J, Ambroise-Thomas P
Département de Parasitologie-Mycologie Médicale et Moléculaire, RHAP, CNRS UPRES A 5082, Université Joseph Fourier-Grenoble I, La Tronche, France.
Clin Exp Immunol. 1998 Feb;111(2):325-33. doi: 10.1046/j.1365-2249.1998.00499.x.
The human platelet contribution against the intracellular growth of the parasite in vitro in human pulmonary fibroblasts was explored. It was observed that tachyzoites of Toxoplasma gondii induced activation of human platelets and additionally that platelets mediated inhibition of intracellular growth in a virulent T. gondii strain. A prominent role for platelet-derived growth factor (PDGF) was demonstrated in this phenomenon, by testing human recombinant PDGF-AA, -AB and -BB and antibodies to human PDGF-AB that partially reversed its effects. Moreover, the effect of PDGF was significantly higher if the host cells were treated 2 h before parasite infection. PDGF was not directly 'toxic' to free tachyzoites, but only affected parasites within host cells. PDGF-mediated inhibition may involve the cyclooxygenase cycle of the fibroblasts being partially reversed by the cyclooxygenase inhibitors, acetylsalicylic acid and indomethacin. However, a thromboxane synthetase pathway was not implicated. PDGF action against intracellular tachyzoites may also include increased IL-6 production in fibroblasts. Finally, transforming growth factor-beta 1 (TGF-beta1), another component of alpha-granules released at the same time as PDGF, may not be antagonistic to the PDGF parasite inhibitory effect in confluent host cells.
研究了人血小板对寄生虫在人肺成纤维细胞中体外细胞内生长的作用。观察到刚地弓形虫速殖子可诱导人血小板活化,此外血小板可介导对强毒株刚地弓形虫细胞内生长的抑制。通过检测人重组血小板衍生生长因子(PDGF)-AA、-AB和-BB以及针对人PDGF-AB的抗体,发现其部分逆转了该效应,从而证明了PDGF在这一现象中起重要作用。此外,如果在寄生虫感染前2小时处理宿主细胞,PDGF的作用会显著增强。PDGF对游离速殖子无直接“毒性”,仅影响宿主细胞内的寄生虫。PDGF介导的抑制作用可能涉及成纤维细胞的环氧化酶循环,该循环可被环氧化酶抑制剂乙酰水杨酸和吲哚美辛部分逆转。然而,血栓素合成酶途径未参与其中。PDGF对细胞内速殖子的作用还可能包括增加成纤维细胞中IL-6的产生。最后,与PDGF同时释放的α-颗粒的另一种成分转化生长因子-β1(TGF-β1),在汇合的宿主细胞中可能不会拮抗PDGF对寄生虫抑制作用。