Lipopolysaccharide-induced lung injury in mice. II. Evaluation of functional damage in isolated parenchyma strips.
Pulmonary inflammatory diseases are characterized by changes in airway responsiveness. This phenomenon is commonly related to the action of inflammatory mediators produced by infiltrated leukocytes. The aim of this study was to investigate in an ex vivo experimental model the effect of acute instillation of lipopolysaccharide (bacterial endotoxin; LPS) on lung parenchyma contractility. We firstly characterized the responsiveness of isolated murine lung to airway stimuli. Murine parenchymal strips were found to be mainly sensitive to 5-hydroxytryptamine (5-HT) while the cholinergic agonist, methacholine (MCh), evoked a smaller contractile response. 5-HT responsiveness was inhibited by methysergide. No significant parenchymal contraction was evoked by histamine, substance P and bradykinin. Lung responsiveness to 5-HT was significantly reduced by in vivo LPS treatment and this effect was only partially paralleled by leukocyte infiltration. In addition, LPS-induced hyporesponsiveness was significantly inhibited by betamethasone (BMS) or pentoxifylline (PTX) pretreatment suggesting that 5-HT lung hyporesponsiveness could be mediated by LPS-induced inflammatory mediators such as inflammatory cytokines.
Brandolini
L
L
Section of Pharmacology, DOMPE S.p.A., L'Aquila, Italy.
Asti
C
C
Ruggieri
V
V
Intilangelo
A
A
Pellegrini
L
L
Chiusaroli
R
R
Caselli
G F
GF
Bertini
R
R
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001623:Betamethasone / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008171:Lung Diseases / Q000139:chemically induced* / Q000503:physiopathology; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D010431:Pentoxifylline / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D016210:Methacholine Chloride; D012701:Serotonin; D013373:Substance P; D006632:Histamine; D001623:Betamethasone; D001920:Bradykinin; D010431:Pentoxifylline