LPS-induced lung injury in neonatal rats: changes in gelatinase activities and consequences on lung growth.
Postnatal lung growth disorders may involve imbalance between metalloproteinases and their inhibitors. Inflammatory cell 92-kDa gelatinase overactivity has been reported in adults with lung injury but has not been looked for in neonates. We compared gelatinase activity in neonatal and adult rats and evaluated postnatal lung growth after lipopolysaccharide (LPS)-induced lung injury. Significant intra-alveolar inflammatory cell recruitment occurred in adults and neonates; cell counts increased 16-fold in adults and 2.7-fold in neonates. Total 92-kDa gelatinase activity was increased in neonates and adults and was significantly correlated to inflammatory cell counts. For a given cell count, 92-kDa gelatinase increased more in neonates than in adults. Morphometric neonatal lung analysis showed that LPS-injured lungs had decreases in absolute values of lung volume (P < 0.03), alveolar surface (P < 0.004), and air space volume (P < 0.03). Doxycycline, a nonspecific metalloproteinase inhibitor, partly inhibited LPS-induced 92-kDa gelatinase overactivity but did not improve LPS-induced alveolar growth disorders. LPS-mediated lung injury in neonatal rats induced both gelatinase B overactivity and alveolar growth disorders, although no causal link between these two effects was demonstrated.
Franco
Marie-Laure
ML
Unité Institut National de la Santé et de la Recherche Médicale U492, Faculté de Médecine, 94000 Créteil, France.
Waszak
Paul
P
Banalec
Gaëlle
G
Levame
Micheline
M
Lafuma
Chantal
C
Harf
Alain
A
Delacourt
Christophe
C
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000009:adverse effects / Q000494:pharmacology; D004357:Drug Synergism; D018093:Gelatinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000254:growth & development; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D011014:Pneumonia / Q000139:chemically induced* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D008070:Lipopolysaccharides; D018093:Gelatinases; D008666:Metalloendopeptidases; D004318:Doxycycline