Mitogenic activity of tracheal effluents from premature infants with chronic lung disease.
Lung injury alters the expression and release of growth factors that disrupt postnatal pulmonary development in newborns and causes chronic lung disease (CLD). The effect of these factors, released into the airways of newborns with CLD, on cell proliferation and collagen production was characterized in vitro. Human fetal lung fibroblast and alveolar-epithelial-like cell lines (FHs 738Lu and A549, respectively) were exposed to tracheal effluents from infants with CLD (mean gestation, 24.7 +/- 0.9 wk; birth weight, 666 +/- 85 g; postnatal age, 0-62 d). In both cell types, proliferation was assessed by measuring [(3)H]-thymidine uptake; in fibroblasts, collagen production was analyzed by measuring [(3)H]-proline incorporation. The activity of specific growth factors in effluents was determined using anti-growth factor antibodies and the growth factors themselves. Growth factors in tracheal effluents promoted proliferation in a dose-dependent manner and caused up to a 10.2- and 3.1-fold increase in thymidine uptake by fibroblasts and epithelial cells, respectively. Collagen production by fibroblasts increased dose dependently, peaking at 177% of baseline. Antibody against transforming growth factor beta-1 (TGF-beta(1)) inhibited proliferation and the increase in collagen production by 31% (p = 0.01) and 14% (p = 0.045), respectively. Antibody against hepatocyte growth factor (HGF) inhibited proliferation of epithelial cells (25%, p = 0.039). The effects of exogenous TGF-beta(1) on fibroblasts and HGF on epithelial cells resembled those of tracheal effluents. Potent mitogenic and differentiating substances are released into the tracheal effluents of newborns with CLD. TGF-beta(1) may worsen CLD by inducing fibrosis whereas HGF may favor resolution by promoting epithelialization.
Saito
Mika
M
Department of Pediatrics, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka 545-8585, Japan.
Ichiba
Hiroyuki
H
Yokoi
Toshiaki
T
Hirai
Chie
C
Yamano
Tsunekazu
T
Kusuda
Satoshi
S
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002908:Chronic Disease; D003094:Collagen / Q000096:biosynthesis; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007234:Infant, Premature; D008171:Lung Diseases / Q000503:physiopathology*; D055370:Lung Injury; D008934:Mitogens / Q000302:isolation & purification* / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014132:Trachea / Q000503:physiopathology*
D006133:Growth Substances; D008934:Mitogens; D003094:Collagen