EXTRACELLULAR ATP REGULATES THE PROLIFERATION OF ALVEOLAR MACROPHAGES

We examined the effects of extracellular ATP on the proliferation and synthesis of DNA by guinea pig alveolar macrophages (AM). AM prolifera ted spontaneously in vitro, their number doubling in 72 h. Such prolif eration was completely inhibited by adding 1 mM ATP to the culture. Th e inhibition was dose dependent. ATP also suppressed the spontaneous s ynthesis of DNA by AM. The inhibitory effect of ATP was not related to cell damage, as the viability and the superoxide anion-generating act ivity of these cells were unaffected by treatment with ATP for 24 h. T he order of potency of the adenosine nucleotides (ATP > ADP > AMP) ref lected the character of the P2 purinoceptor. Theophyliine inhibited th e effect of ATP on the synthesis of DNA by AM to a level produced by t he nonhydrolyzable analogue, ATPgammaS, but did not influence the effe ct of ATPgammaS. These data suggest that the effect of ATP on the synt hesis of DNA was exerted mainly via the P2 purinoceptor (82.0%) and to a lesser extent via the P1 purinoceptor (12.6%). We found that small molecules in the lavage fluid inhibited the synthesis of DNA by AM. Th us, the extracellular ATP present in the alveolar lining fluid may par ticipate in controlling the proliferation of AM.