Maternal Tobacco Smoking and Lung Epithelium-Specific Proteins in Amniotic Fluid

Abstract

The bronchiolar 16 kD Clara cell secretory protein (CC16) and the alveolar surfactant-associated protein A (SP-A) are secreted in the amniotic fluid (AF), where they reflect the growth and the maturity of the fetal lung. To evaluate the possible effects of in utero tobacco smoke exposure upon infant bronchoalveolar epithelium function and maturity, CC16 and SP-A levels were determined in AF obtained at term (36 -41 wk) from 28 nonsmoking, 18 smoke-exposed, and 28 smoking mothers with uncomplicated pregnancies. Tobacco smoke exposure was assessed by questionnaire and the assay in AF and maternal urine of cotinine, a stable nicotine metabolite. The specificity of the changes of CC16 and SP-A concentrations in AF was assessed by comparison with nonpulmonary proteins of high-(albumin and transferrin) or low-molecular weight (␤ 2 -microglobulin, retinol binding protein, cystatin-C). Pulmonary and nonpulmonary AF proteins were also compared by two-dimensional gel electrophoresis between smoking and nonsmoking mothers. The levels of CC16 and SP-A as well as low-and high-molecularweight proteins were not significantly different between the three smoking categories. The protein pattern of AF, established by two-dimensional gel electrophoresis, did not reveal any quantitative or qualitative difference between nonsmoking (n ϭ 10), smoke-exposed (n ϭ 5), and smoking mothers (n ϭ 5). By multiple regression analysis of possible determinants, tobacco smoke did not emerge as a significant predictor of CC16 and SP-A concentrations in AF. SP-A level was dependent only on gestational age at birth (r 2 ϭ 0.1, p ϭ 0.001), whereas CC16 correlated only with the levels of low-molecular weight proteins (r 2 ϭ 0.2, p ϭ 0.0001). The latter correlation suggests that CC16 enters AF not only as a result of its secretion at the surface of the respiratory tract but also partly following its elimination by the fetal kidney. This study suggests that maternal smoking during pregnancy is not associated with alterations of the secretory functions of the epithelium of the distal airways and the alveoli at term. Maternal smoking during pregnancy is associated with an increased incidence of respiratory illnesses for children during infancy and later in childhood (1-3). Impaired airway function has also been described in both term and preterm infants of smoking mothers, suggesting that maternal smoking probably alters airway and alveolar growth during fetal life (4 -7). No causal mechanisms for these clinical and functional effects have so far been clearly delineated.The pulmonary epithelium is a major target of injury by tobacco smoke toxicants in adults. Some of these toxicants with lipophilic properties are transferred from the mother to the fetus through the placenta (8, 9) and are likely bioactivated in more toxic compounds by fetal pulmonary epithelial cells (10). One may therefore hypothesize that maternal smoking might alter in utero the development and secretory functions of epithelial cells lining the fetal airways and alveoli.Recently, the m...

In utero nicotine exposure alters fetal rat lung alveolar type II cell proliferation, differentiation, and metabolism

“…However, Wuenschell et al (35) reported significant increases in the expression of SP-A and -C mRNAs in a murine developing lung explant model. Hermans et al (11) did not find any significant differences in amniotic fluid SP-A levels at full term in smoke-exposed vs. non-smoke-exposed pregnancies. The conflicting results in these studies are likely to be related to differences in the models used (species and stage of lung development), duration of nicotine exposure (acute vs. chronic), whether smoke or nicotine was used as a challenge, and the end points, for example, whether phospholipid synthesis, secretion, or total pool size was examined.…”

Club Cell Protein 16 (CC16) Augmentation: A Potential Disease-modifying Approach for Chronic Obstructive Pulmonary Disease (COPD)

“…A randomized, placebo-controlled clinical trial of a single dose of rCC16 delivered by the intra-tracheal route to premature infants with respiratory distress syndrome having low CC16 levels in tracheal aspirate fluid (TAF) samples showed that this therapy was well tolerated, and resulted in a significant reduction in leukocyte counts and a strong trend towards reduced IL-6 levels in TAF samples 62 . Interestingly, prenatal exposure to CS is associated with decreased expression of CC16 in fetal rat lungs 67 , but this correlation has not been confirmed in human neonates 68 .…”

Effects of nicotine on pulmonary surfactant proteins A and D in ovine lung epithelia

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