Dimethyl sulfoxide decreases lung neutrophil sequestration and lung leak.
To investigate basic mechanisms of acute edematous lung injury (adult respiratory distress syndrome), the formylated tripeptide formyl-norleucyl-leucyl-phenylalanine (FNLP) was instilled intratracheally into hamsters. Intratracheal FNLP produced time-dependent and dose-dependent increases in neutrophils recoverable by lung lavage (neutrophil alveolitis) and leak of intravenously injected albumin into the extravascular lung space (lung leak). Treatment with dimethyl sulfoxide (DMSO) decreased (p less than 0.05) neutrophil alveolitis and lung leak in hamsters given FNLP intratracheally. The effect of DMSO on various neutrophil functions was also studied in vitro. Addition of DMSO at concentrations (about 0.20%) measured in plasma of hamsters given DMSO decreased (p less than 0.05) neutrophil chemotaxis but not neutrophil superoxide anion generation or adherence to cultured endothelial cell monolayers or nylon fiber in vitro. We conclude that intratracheal FNLP causes neutrophil alveolitis and lung leak and that DMSO treatment ameliorates these processes, possibly by inhibiting neutrophil chemotaxis.
Leff
J A
JA
Webb-Waring Lung Institute, Denver, CO 80262.
Oppegard
M A
MA
McCarty
E C
EC
Wilke
C P
CP
Shanley
P F
PF
Day
C E
CE
Ahmed
N K
NK
Patton
L M
LM
Repine
J E
JE
D000818:Animals; D001792:Blood Platelets / Q000648:ultrastructure; D001992:Bronchoalveolar Lavage Fluid / Q000473:pathology; D006224:Cricetinae; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D008297:Male; D008647:Mesocricetus; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009842:Oligopeptides / Q000633:toxicity*; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000503:physiopathology
D009842:Oligopeptides; C024998:N-formylnorleucyl-leucyl-4-phenylalanine; D004121:Dimethyl Sulfoxide