STIMULATION OF THE RAT ALVEOLAR MACROPHAGE RESPIRATORY BURST BY EXTRACELLULAR ADENINE-NUCLEOTIDES

Exogenous nucleotides can serve as extracellular factors that cause si gnificant functional changes in numerous cells, including phagocytes. In the current study, addition of ATP, ADP, and ATPgammaS directly sti mulated the respiratory burst (superoxide production) by rat alveolar macrophages, whereas adenosine and AMP did not. The relative potency o f these nucleotides at saturating concentration was ADP greater-than-o r-equal-to ATPgammaS > > ATP; however, simultaneous addition of maxima lly stimulatory concentrations of ADP and ATP (100 muM of each) produc ed an additive effect suggesting involvement of two P2 receptors. Foll owing addition of the nucleotides, an elevation of intracellular Ca2([Ca2+]i) occurred within seconds, followed by a decline within 1 min but with a prolonged elevation above baseline for at least 5 min. Remo val of extracellular Ca2+ only slightly attenuated the initial elevati on, indicating that adenine nucleotides stimulate the rapid release of intracellular Ca2+ stores. Removal of extracellular Ca2+ also elimina ted the sustained elevation in [Ca2+]i and markedly suppressed the res piratory burst. Incubation with verapamil, a Ca2+ channel blocker, als o significantly inhibited the respiratory burst stimulated by ATR Thes e studies demonstrate that adenine nucleotides stimulate a Ca2+-depend ent respiratory burst by rat alveolar macrophages, probably through pu rinergic receptors.