Role of P2z purinergic receptors in ATP-mediated killing of tumor necrosis factor (TNF) -sensitive and TNF-resistant L929 fibroblasts
Pizzo, P.; Murgia, M.; Zambon, A.; Zanovello, P.; Bronte, V.; Pietrobon, D.; Di Virgilio, F.
Journal of Immunology 149(10): 3372-3378
1992
ISSN/ISBN: 0022-1767 PMID: 1431111 Document Number: 402876
Two closely related cell lines were characterized in their responses to extracellular ATP (ATP-o): the fibroblast cell line L929 and TNF-resistant variant L929/R. Both lines showed ATP-o-activated increases in intracellular Ca-2+, inward current, and sustained depolarization of the plasma membrane, cell responses compatible with activation of purinegic receptors of the P2y, P2x, or P2z subype; however, only the L929/R variant was susceptible to ATP-o-dependent early permeabilization of the plasma membrane to hydrophilic solutes of M-r below 900, a response uniquely caused by the activation of P-2z receptors. Both cell types were susceptible to the cytotoxic effect of ATP-o, but killing of the L929/Rs variant required much shorter incubations in the presence of this nucleotide. Morphologic examination of ATP-o-challenged L929 and L929/R cells showed that cell death occurred by two alternative mechanisms: colloido-osmotic lysis or apoptosis. Occurrence of apoptosis was confirmed by agarose gel analysis of cellular DNA. Although ATP-o caused a fast mobilization of intracellular Ca-2+ dependent. Our results show that the L929/r variant, but not the L929 parental fibroblast cell line, expresses functional purinergic receptors of the P-2z subtype. The presence of P-2z receptors confers to L929/R cells enhanced susceptibility to ATP-o-mediated cytotoxicity.