ATP-MEDIATED CYTOTOXICITY IN MICROGLIAL CELLS

Microglial cells are known to express purinergic receptors for extrace llular ATP of both the P2Y and P2X subtypes. Functional studies have s hown that both primary mouse microglial cells and the N9 and N13 micro glial cell lines express the pore-forming P2Z/P2X(7) receptor. Here we identify the presence of this receptor in N9 and N13 cells with a spe cific polyclonal Ab and show that microglial cells expressing the P2Z/ P2X(7) receptor are exquisitively sensitive to ATP-mediated cytotoxici ty while clones selected for the lack of this receptor are resistant. Transfection of HEK293 cells with P2X(7) (but not P2X(2)) receptor cDN A confers susceptibility to ATP-mediated cytotoxicity. Morphological a nd biochemical analysis suggests that ATP-dependent cell death in micr oglial cells occurs by apoptosis. Finally, microglial cells release AT P via a nonlytic mechanism when activated by bacterial endotoxin, thus suggesting the operation of a purinergic autocrine/paracrine loop. (C ) 1997 Elsevier Science Ltd.