Extracellular ATP stimulates elastase secretion from human neutrophils and increases lung resistance and secretion from normal rat airways after intratracheal instillation.
The effect of ATP on intracellular Ca2+ levels and elastase secretion in isolated normal human peripheral blood neutrophils was investigated as was its in vivo effect on lung resistance and mucous secretion. ATP (10(-5) M) increased [Ca2+]i from 61 +/- 3 to 165 +/- 15 nM in nonactivated neutrophils; elastase secretion was increased by 40% from nonactivated neutrophils but was unaffected in fMLP (10(-5) M) activated cells. Instillation of ATP (10(-5) and 10(-3) M) into the airways of brown Norway rats increased both lung resistance and secretion. These findings suggest that aerosolization of ATP into the cystic fibrosis-affected bronchial tree might be hazardous in terms of enhancement of parenchymal damage, which would result from neutrophil elastase release, and in terms of impaired respiratory lung function.
Flezar
M
M
CF Research Lab, Montréal Chest Hospital, Qué., Canada.
Olivenstein
R
R
Cantin
A
A
Heisler
S
S
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D006801:Humans; D066298:In Vitro Techniques; D007442:Intubation, Intratracheal; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000378:metabolism*; D051381:Rats; D011914:Rats, Inbred BN
D009240:N-Formylmethionine Leucyl-Phenylalanine; D000255:Adenosine Triphosphate; D010196:Pancreatic Elastase