Human platelet inhibition of Toxoplasma gondii growth.
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.
Chumpitazi
B F
BF
Département de Parasitologie-Mycologie Médicale et Moléculaire, RHAP, CNRS UPRES A 5082, Université Joseph Fourier-Grenoble I, La Tronche, France.
Simon
J
J
Polack
B
B
Peyron
F
F
Picot
S
S
Ricard
J
J
Ambroise-Thomas
P
P
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D000081008:Bicyclic Monoterpenes; D001792:Blood Platelets / Q000276:immunology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D015539:Platelet Activation / Q000276:immunology; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014122:Toxoplasma / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D014498:Uracil / Q000493:pharmacokinetics
D000081008:Bicyclic Monoterpenes; D007093:Imidazoles; D007328:Insulin; D015850:Interleukin-6; D010982:Platelet-Derived Growth Factor; D014498:Uracil; D013928:Thromboxane A2; C031572:1-carboxyheptylimidazole; C020465:pinane-thromboxane A2; D001241:Aspirin