Stimulation of the Rat Alveolar Macrophage Respiratory Burst by Extracellular Adenine Nucleotides
1993; American Thoracic Society; Volume: 9; Issue: 5 Linguagem: Inglês
10.1165/ajrcmb/9.5.505
ISSN1535-4989
AutoresJudith K. Murphy, F. R. Livingston, Evelyne Gozal, Martine Torrès, Henry Jay Forman,
Tópico(s)Genetics and Neurodevelopmental Disorders
ResumoExogenous nucleotides can serve as extracellular factors that cause significant functional changes in numerous cells, including phagocytes. In the current study, addition of ATP, ADP, and ATPγS directly stimulated the respiratory burst (superoxide production) by rat alveolar macrophages, whereas adenosine and AMP did not. The relative potency of these nucleotides at saturating concentration was ADP ≥ ATPγS > > ATP; however, simultaneous addition of maximally stimulatory concentrations of ADP and ATP (100 µM of each) produced an additive effect suggesting involvement of two P2 receptors. Following 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. Removal of extracellular Ca2+ only slightly attenuated the initial elevation, indicating that adenine nucleotides stimulate the rapid release of intracellular Ca2+ stores. Removal of extracellular Ca2+ also eliminated the sustained elevation in [Ca2+]i and markedly suppressed the respiratory burst. Incubation with verapamil, a Ca2+ channel blocker, also significantly inhibited the respiratory burst stimulated by ATP. These studies demonstrate that adenine nucleotides stimulate a Ca2+-dependent respiratory burst by rat alveolar macrophages, probably through purinergic receptors.
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