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Infection and Immunity, August 2002, p. 4424-4432, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4424-4432.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

ADP and Other Metabolites Released from Acanthamoeba castellanii Lead to Human Monocytic Cell Death through Apoptosis and Stimulate the Secretion of Proinflammatory Cytokines

A. Mattana,1* V. Cappai,1 L. Alberti,1 C. Serra,2 P. L. Fiori,2 and P. Cappuccinelli2

Department of Pharmaceutical Sciences,1 Department of Biomedical Sciences Division of Experimental and Clinical Microbiology, University of Sassari, 07100 Sassari, Italy2

Received 10 January 2002/ Returned for modification 4 March 2002/ Accepted 7 May 2002

Monocytes/macrophages are thought to be involved in Acanthamoeba infections. The aim of this work was to study whether soluble metabolites (ADP and other compounds) released by Acanthamoeba castellanii trophozoites could induce morphological and biochemical changes in human monocytic cells in vitro. We demonstrate here that ADP constitutively released in the medium by A. castellanii, interacting with specific P2y2 purinoceptors expressed on the monocytic cell membrane, caused a biphasic rise in [Ca2+]i, morphological changes characteristics of cells undergoing apoptosis, caspase-3 activation, and secretion of tumor necrosis factor alpha (TNF-{alpha}). The same results were found in monocytes exposed to purified ADP. Cell damage and TNF-{alpha} release induced by amoebic ADP were blocked by the P2y2 inhibitor suramin. Other metabolites contained in amoebic cell-free supernatants, with molecular masses of, respectively, >30 kDa and between 30 and 10 kDa, also caused morphological modifications and activation of intracellular caspase-3, characteristics of programmed cell death. Nevertheless, mechanisms by which these molecules trigger cell damage appeared to differ from that of ADP. In addition, other amoebic thermolable metabolites with molecular masses of <10 kDa caused the secretion of interleukin-1ß. These findings suggest that pathogenic free-living A. castellanii by release of ADP and other metabolites lead to human monocytic cell death through apoptosis and stimulate the secretion of proinflammatory cytokines.

* Corresponding author. Mailing address: Dipartimento di Scienze del Farmaco, Via Muroni 23/A, 07100 Sassari, Italy. Phone: 39-079-228744/228711. Fax: 39-079-228712. E-mail: dsfanto{at}ssmain.uniss.it.

Editor: W. A. Petri, Jr.

Infection and Immunity, August 2002, p. 4424-4432, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4424-4432.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Mattana, A., Alberti, L., Delogu, G., Fiori, P. L., Cappuccinelli, P. (2009). In Vitro Activity of Acanthamoeba castellanii on Human Platelets and Erythrocytes. Infect. Immun. 77: 733-738 [Abstract] [Full Text]  
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