Retinoic acid does not affect alveolar septation in adult FVB mice with elastase-induced emphysema.
BACKGROUND
Administration of ALL-TRANS retinoic acid (ATRA) to adult Sprague-Dawley rats with emphysema induced by porcine pancreatic elastase (PPE) reversed the emphysema perhaps by inducing new alveolar formation.


OBJECTIVE
A study was conducted to determine whether ATRA can induce new alveolar septa and reverse the airspace enlargement caused in adult mice by PPE treatment.


METHODS
48 FVB mice were divided into 6 groups. Three groups received 15 microg of PPE in 0.1 ml of 0.9% saline and 3 groups received 0.1 ml of saline, intratracheally. Starting at day 22, the mice received 12 daily intraperitoneal injections of cottonseed oil, with or without ATRA (12.5 microg or 50 microg). The mice were killed for study 1 day after the last injection.


RESULTS
Measurements of plasma and lung tissue ATRA levels showed statistically significant elevated levels after the 50-microg but not after the 12.5-microg doses of ATRA. In situ hybridization studies of elastin and alpha(1)(I) collagen mRNA expression in pulmonary parenchyma as well as in airways and blood vessels showed no effect of ATRA. Airspace size was determined by the mean linear intercept (Lm) method. The Lm of the groups receiving PPE and ATRA (46.2 +/- 4.1 microm, mean +/- SD) was not significantly different from the group receiving PPE and oil (47.8 +/- 6.0 microm). The Lm for groups receiving saline and ATRA (40.6 +/- 2.5 microm) were not significantly different from the group receiving saline and oil (41.0 +/- 2.7 microm). Comparison of the fixed lung volume data and calculated internal surface area also showed no differences between the control and ATRA-treated groups.


CONCLUSIONS
ATRA treatment does not affect airspace size or expression of elastin or alpha(1)(I) collagen mRNA in adult FVB mice with PPE-induced emphysema.
Lucey
Edgar C
EC
Boston VA Medical Center, Boston, Massachusetts 02130, USA. edlucey@bu.edu
Goldstein
Ronald H
RH
Breuer
Raphael
R
Rexer
Brent N
BN
Ong
David E
DE
Snider
Gordon L
GL
D000818:Animals; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008168:Lung / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D010196:Pancreatic Elastase / Q000009:adverse effects; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000254:growth & development; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000188:drug therapy; D014212:Tretinoin / Q000494:pharmacology*
D014212:Tretinoin; D010196:Pancreatic Elastase