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Am J Physiol Cell Physiol 276: C1139-C1147, 1999;
0363-6143/99 $5.00
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Vol. 276, Issue 5, C1139-C1147, May 1999

P2Z/P2X7 receptor-dependent apoptosis of dendritic cells

Robson Coutinho-Silva1, Pedro M. Persechini2, Rodrigo Da Cunha Bisaggio2, Jean-Luc Perfettini1, Ana Cristina Torres De Sa Neto2, Jean M. Kanellopoulos3, Iris Motta-Ly3, Alice Dautry-Varsat1, and David M. Ojcius1

1 Unité de Biologie des Interactions Cellulaires, Centre National de la Recherche Scientifique 1960, and 3 Unité de Biologie Moléculaire du Gène, Institut National de la Santé et de la Recherche Médicale 277, Institut Pasteur, Paris, France; and 2 Laboratorio de Imunobiofisica, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

Macrophages and thymocytes express P2Z/P2X7 nucleotide receptors that bind extracellular ATP. These receptors play a role in immune development and control of microbial infections, but their presence on dendritic cells has not been reported. We investigated whether extracellular ATP could trigger P2Z/P2X7 receptor-dependent apoptosis of dendritic cells. Apoptosis could be selectively triggered by tetrabasic ATP, since other purine/pyrimidine nucleotides were ineffective, and it was mimicked by the P2Z receptor agonist, benzoylbenzoyl ATP, and blocked by magnesium and the irreversible antagonist, oxidized ATP. RT-PCR analysis confirmed the mRNA expression of the P2Z/P2X7 receptor and the absence of P2X1. Caspase inhibitors and cycloheximide had only a partial effect on the apoptosis, suggesting that a caspase-independent mechanism may also be operative. Brief treatment with ATP led to an increase in the intracellular calcium concentration and permeabilization of the plasma membrane to Lucifer yellow, which diffused throughout the dendritic cell cytosol. Other small extracellular molecules may thus attain a similar intracellular distribution, perhaps activating endogenous proteases that contribute to initiation of apoptosis.

adenosine 5'-triphosphate; inflammatory mediators


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