LPS-induced lung injury in neonatal rats: changes in gelatinase activities and consequences on lung growth

Franco, Marie-Laure; Waszak, Paul; Banalec, Gaëlle; Levame, M; Lafuma, C.; Harf, Alain; Delacourt, Christophe

doi:10.1152/ajplung.00140.2001

Cited by 36 publications

(40 citation statements)

References 39 publications

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“…Thus MMP-9 may be considered as an important marker of the initial inflammatory response, but its contribution to the development of long-term sequel is uncertain. These findings are in complete agreement with our laboratory's recent experiments performed in newborn rats (14). Indeed, we found that alveolar growth disorders induced by intratracheal instillation of lipopolysaccharide were associated with alveolar neutrophil influx and increased MMP-9 level, but we failed to prevent growth disorders by inhibiting MMP-9 activity.…”

Section: Discussionsupporting

confidence: 93%

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Gelatinase activities in the airways of premature infants and development of bronchopulmonary dysplasia

Danan

Jarreau

Franco

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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2002.-Matrix-degrading metalloproteinases may play a role in the pathophysiology of bronchopulmonary dysplasia (BDP). We, therefore, evaluated correlations between gelatinase activities [metalloproteinase (MMP)-2 and MMP-9] or tissue inhibitor of metalloproteinase (TIMP)-1 levels present in the airways during the initial phase of hyaline membrane disease and the onset of BPD. Tracheal aspirates were obtained within 6 h of birth (day 0) from 64 intubated neonates with a gestational age Յ30 wk. Forty-five neonates were resampled on day 3 or 5. Total MMP-2 level measured by zymography fell with time, whereas total MMP-9 level and TIMP-1 levels, assayed by ELISA, increased; the MMP-9 increase correlated with the increase in airway inflammatory cell numbers. Among the parameters measured on day 0, 3, or 5, lower total MMP-2 level, lower birth weight, and higher fraction of inspired oxygen on day 0 were significantly and independently associated with the development of BPD. In conclusion, MMP-9 level and TIMP-1 levels increased after birth but are not linked to BPD outcome. In contrast, low MMP-2 level at birth is strongly associated with the development of BPD. metalloproteinase; lung development; newborn; extracellular matrix PREMATURE NEONATES WITH HYALINE membrane disease are at risk of developing bronchopulmonary dysplasia (BPD), as a sequel of both the disease and its treatment. The pathogenesis is unclear, but BPD is thought to result from damage to an immature lung. Mechanical ventilation, oxygen therapy, and airway inflammatory responses have all been implicated in the development of BPD (19). These insults appear to interfere with normal lung maturation, which is incomplete at birth. In particular, they appear to alter alveolar formation, on the basis of morphometric studies of severe BPD (3, 24). Alveolar formation is characterized by the multiplication of alveolar septa and the thinning of interalveolar walls, both of which require intense remodeling of the pulmonary extracellular matrix (4). Changes in matrix turnover have been experimentally linked to abnormal alveolar formation (20). The proteinase-antiproteinase balance in the lung is a key factor in harmonious matrix turnover. In particular, matrix metalloproteinases (MMPs), which can synergistically digest the major macromolecules of connective tissue matrices, have been implicated in physiological regulation of lung growth. The MMP gelatinase A (MMP-2) has been shown to play a role in the major collagen turnover that occurs during early postnatal rat lung growth (1, 2). We postulated that MMP-2 might also participate in human lung development and that inadequate MMP-2 levels in premature lungs exposed to insults could contribute to impaired lung growth and thus to BPD. We also postulated that MMPs may be secreted in excess during the inflammatory response associated with hyaline membrane disease and may, therefore, lead to tissue degradation. Gelatinase B (MMP-9) is the main MMP released by inflammatory cells such as neutrophils and alveolar macroph...

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Section: Discussionsupporting

confidence: 93%

“…Once secreted, MMP-9 can be activated by many products present in inflammatory airways, especially oxidants (29) and neutrophil elastase (34). In our study, the presence and amount of (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) Values are medians with 25th-75th percentiles in parentheses; n, no. of neonates.…”

Section: Discussionmentioning

confidence: 73%

Gelatinase activities in the airways of premature infants and development of bronchopulmonary dysplasia

Danan

Jarreau

Franco

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…20 fields per animal) selected by systematic sampling from a random starting point to ensure that the sections were randomly distributed throughout all of the lung lobes. We used a correcting factor of 1.22 to correct the surface area values for the shrinkage caused by our fixation and paraffin-embedding procedure (20). Using the point and intersection counting method (19) …”

Section: Methodsmentioning

confidence: 99%

Effect of Nω-Nitro-l-Arginine Methyl Ester–Induced Intrauterine Growth Restriction on Postnatal Lung Growth in Rats

2005

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Infants with intrauterine growth restriction (IUGR) are at high risk for morbidity and mortality. Preeclampsia, one of the leading causes of IUGR, begins during the canalicular phase of lung development. The aim of our study was to determine whether induced IUGR was responsible for abnormal lung development in rat pups. We randomized pregnant Sprague-Dawley rats to daily gavage with either the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME; n ϭ 5, 50 mg · kg Ϫ1 · dϪ1 ) or pure water (n ϭ 6). The pups were weighed at birth and on postnatal days 7 and 14. At each of these time points, pups were killed and their lung growth was assessed on the basis of lung volume and light-microscopy morphometric data. At birth, body weight, total alveolar surface area, and alveolar surface density were significantly decreased and alveolar size was significantly increased in the L-NAME group, compared with the control group. On day 7, body weight was similar in the two groups, and the only significant difference was smaller total alveolar surface area in the L-NAME group. On day 14, neither body weight nor lung morphometric parameters were significantly different between the L-NAME group and the controls. These results suggest that postnatal catch-up growth may completely correct the lung development disorders present at birth in IUGR pups, in parallel with the catch-up body weight gain. Studies have established that intrauterine growth restriction (IUGR) is correlated with increased morbidity and mortality (1-3). Despite the huge strides made in neonatal medicine over the past 15 y, the risk for respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis, as well as length of stay and hospital costs, remain higher in growth-restricted newborns (3). Importantly, the adverse effects of IUGR are long lasting, one of the most common long-term consequences being respiratory disease (4 -7).Preeclampsia is among the leading causes of IUGR. The placental vascular abnormalities associated with preeclampsia impair maternofetal exchanges, thereby restricting fetal growth (8). Impairments in maternofetal exchanges begin during the third trimester of pregnancy, during which lung development is at the canalicular phase, characterized by formation of the distal airways, blood vessels, and alveolar-capillary barrier (9).Although the pathophysiology of preeclampsia remains unclear, experimental evidence points to a key role for nitric oxide (NO) (10 -13). NO synthase (NOS) inhibition during the last third of pregnancy in rats was followed by hypertension and proteinuria in the dams and by IUGR and high fetal mortality in the offspring, a combination that replicated preeclampsia in humans (14 -16). In rats, IUGR induced by NOS inhibition was associated with hindlimb necrosis at birth (17). To our knowledge, the long-term development of the offspring was not documented. These data prompted us to assess whether lung development was impaired in rat pups with IUGR induced by NOS inhibition in the ...

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“…Morphometric evaluations were repeated by a second independent observer in order to test reproducibility. To correct for shrinkage associated with fixation and paraffin processing, area values were multiplied by 1.22, a factor calculated during a previous evaluation [17]. All morphometric data were expressed as relative and absolute values, as described by BURRI et al [18].…”

Section: Assessment Of Lung Morphometrymentioning

confidence: 99%

“…Assessment of inflammation BAL BAL was performed as previously described [17]. Briefly, rabbits were exsanguinated and the thorax was opened to expose the lungs and trachea.…”

Section: Assessment Of Lung Morphometrymentioning

confidence: 99%

Antenatal infection in the rabbit impairs post-natal growth and lung alveolarisation

Guen¹,

Denis²,

Franco-Montoya³

et al. 2008

European Respiratory Journal

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Clinical and experimental studies indicate an association between chorioamnionitis and bronchopulmonary dysplasia in preterm infants. The present authors hypothesised that, in the rabbit, antenatal infection may impair lung development after birth, despite effective maternal antibiotic therapy.Pregnant rabbits received an intra-uterine inoculation of 10 3 Escherichia coli colony forming units or vehicle at the end of gestation (day 29). Intravenous ceftriaxone therapy was initiated 8 h after inoculation for a period of 8 days. Pups born between 60 and 84 h after inoculation were kept with their mother until sacrifice on days 0, 1, 5, 8 and 15. Blood cultures from antenatally infected animals were sterile at birth. Postnatal growth was significantly impaired by day 8. Lung morphometry showed a significant decrease of alveolar surface density and interstitial density, with a significant increase of alveolar airspace volume, indicating impaired alveolarisation for the first 2 weeks of postnatal life. Inflammatory and apoptotic processes were not detected in the lung at birth or subsequently.Intra-uterine infection in rabbits is, therefore, responsible for concomitant postnatal growth retardation and abnormal pulmonary development despite early and effective antenatal antibiotic therapy. This may constitute an alternative model to study the consequences of antenatal infection on postnatal growth and lung development.

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LPS-induced lung injury in neonatal rats: changes in gelatinase activities and consequences on lung growth

Cited by 36 publications

References 39 publications

Gelatinase activities in the airways of premature infants and development of bronchopulmonary dysplasia

Gelatinase activities in the airways of premature infants and development of bronchopulmonary dysplasia

Effect of Nω-Nitro-l-Arginine Methyl Ester–Induced Intrauterine Growth Restriction on Postnatal Lung Growth in Rats

Antenatal infection in the rabbit impairs post-natal growth and lung alveolarisation

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