Am. J. Respir. Cell Mol. Biol., Vol 10, No. 5, 05 1994, 560-564.
Extracellular ATP regulates the proliferation of alveolar macrophages
M Nakanishi, M Kawasaki, H Ogino, M Yoshida and K Yagawa
Second Department of Internal Medicine, Faculty of Medicine, Fukuoka University, Japan.
We examined the effects of extracellular ATP on the proliferation and
synthesis of DNA by guinea pig alveolar macrophages (AM). AM proliferated
spontaneously in vitro, their number doubling in 72 h. Such proliferation
was completely inhibited by adding 1 mM ATP to the culture. The inhibition
was dose dependent. ATP also suppressed the spontaneous synthesis of DNA by
AM. The inhibitory effect of ATP was not related to cell damage, as the
viability and the superoxide anion- generating activity of these cells were
unaffected by treatment with ATP for 24 h. The order of potency of the
adenosine nucleotides (ATP > ADP > AMP) reflected the character of
the P2 purinoceptor. Theophylline inhibited the effect of ATP on the
synthesis of DNA by AM to a level produced by the nonhydrolyzable analogue,
ATP gamma S, but did not influence the effect of ATP gamma S. These data
suggest that the effect of ATP on the synthesis 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. Thus, the extracellular ATP present
in the alveolar lining fluid may participate in controlling the
proliferation of AM.
