Activation of polymorphonuclear leukocytes in oleic acid-induced lung injury.
OBJECTIVE
Oleic acid (OA) can produce a lung injury similar to the adult respiratory distress syndrome (ARDS). Elastase and superoxides are thought to have an effect in ARDS. However, the effect that elastase and superoxide have in OA lung injury is unclear. To examine their involvement in OA lung injury, we tested the effects of methoxysuccinyl-alanyl-alanyl-prolyl-valyl chloromethyl ketone (MAAPVCK), an elastase inhibitor, and N-acetyl-L-cysteine (NAC), an active oxygen scavenger, on the increase in pulmonary vascular permeability caused by OA. We also examined whether OA stimulated elastase and/or superoxide release from polymorphonuclear leukocytes (PMNs).


METHODS
Prospective trial.


METHODS
University laboratory.


METHODS
(1) Guinea pigs were anesthetized. MAAPVCK (2.5 mg/ kg) or NAC (150 mg/kg) was infused over OA (15 microl/kg) injection. Evans blue was used to measure vascular permeability. (2) PMNs were isolated from the blood of guinea pigs and rats. Elastase release was measured with MeO-Suc-Ala-Ala-Pro-Val-7-amino-4-methylcoumarin. Superoxide production was measured by the ferricytochrome c reduction method.


RESULTS
OA caused pulmonary hemorrhage and an increase in vascular permeability. MAAPVCK and NAC significantly attenuated the increase in vascular permeability in distal bronchus and trachea, respectively. OA induced superoxide production from PMNs in guinea pigs, but elastase release from PMNs was not detected.


CONCLUSIONS
These results suggest that elastase and superoxide are involved in OA lung injury.
Department of Pathopharmacology, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan. moriuchi@gpo.kumamoto-u.ac.jp
H
H
Moriuchi
M
M
Zaha
T
T
Fukumoto
T
T
Yuizono
D000111:Acetylcysteine / Q000494:pharmacology*; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006168:Guinea Pigs; D019272:Leukocyte Elastase / Q000187:drug effects / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000276:immunology*; D019301:Oleic Acid; D011446:Prospective Studies; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D012128:Respiratory Distress Syndrome / Q000139:chemically induced* / Q000188:drug therapy / Q000276:immunology*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013481:Superoxides / Q000276:immunology
D000590:Amino Acid Chloromethyl Ketones; D016166:Free Radical Scavengers; D015842:Serine Proteinase Inhibitors; D013481:Superoxides; C058167:methoxysuccinyl-alanyl-alanyl-prolyl-alanine chloromethyl ketone; D019301:Oleic Acid; D019272:Leukocyte Elastase; D000111:Acetylcysteine