Serum and BAL Clara cell 10 kDa protein (CC10) levels and CC10-positive bronchiolar cells are decreased in smokers

Shijubo, Noriharu; Itoh, Yoshio; Yamaguchi, Tsutomu; Shibuya, Yoshie; Morita, Yuji; Hirasawa, Michio; Okutani, Ryuta; Kawai, Tadashi; Abe, Shosaku

doi:10.1183/09031936.97.10051108

Cited by 145 publications

(168 citation statements)

References 33 publications

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“…This is in contrast with the well-documented effect of tobacco smoking on the lungs of smokers who exhibit a marked reduction of Clara cell number and decreased levels of CC16 in sputum, bronchoalveolar lavage fluid, and serum (18,19,44). This sensitivity of Clara cells to tobacco smoke injury might result from to the cytochrome-P-450 -mediated metabolic activation, particularly active in Clara cells, of chemicals present in tobacco smoke (19,45).…”

Section: Fetal Lung Epithelium Proteins and Maternal Smokingcontrasting

confidence: 52%

“…This time course and the decreased levels of CC16 and SP-A in AF from fetuses with diaphragmatic hernia and diabetic pregnancy, two situations leading to lung hypoplasia or immaturity, suggest that these proteins in AF might be good indices of the development of fetal airways and alveoli (12,16,17). Clara cells are also known to be very sensitive to a number of air pollutants, including tobacco smoke (18,19). Finally, both proteins have important properties by which they protect the respiratory tract from aggressions (20,21).…”

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confidence: 99%

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

et al. 2001

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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...

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Section: Fetal Lung Epithelium Proteins and Maternal Smokingcontrasting

confidence: 52%

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confidence: 99%

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

et al. 2001

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“…The variables to be included in the multivariable models (age, sex, and current exposure to SHS) were selected a priori based on the published literature. 12,26,37 Due to the relatively small sample size, more variables in the same multivariable models could not be included, but additional analysis replacing current exposure to SHS with other potential confounders (such as maternal asthma or BSS) did not change the results (data not shown). Urine levels of CC16 could be also affected by several other factors (e.g., post-renal excretion of CC16, diurnal variation, and physical activity).…”

Section: Discussionmentioning

confidence: 99%

“…The variables to be included in the multivariable models (infant's age, sex, and current exposure to SHS) were selected a priori based on published literature. 12,26,29,37 First-order interactions were tested for between urine levels of CC16 and each of the covariates mentioned above.…”

Section: Statistical Analysesmentioning

confidence: 99%

Urine Club Cell 16-kDa Secretory Protein and Childhood Wheezing Illnesses After Lower Respiratory Tract Infections in Infancy

Rosas‐Salazar

Gebretsadik

Carroll

et al. 2015

Pediatric Allergy, Immunology, and Pulmonology

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Background: Infants with lower respiratory tract infections (LRTIs) are at an increased risk of developing childhood wheezing illnesses (including asthma), but it is not currently possible to predict those at risk for these long-term outcomes. The current objective was to examine whether urine levels of club cell 16-kDa secretory protein (CC16) at the time of an infant LRTI are associated with the development of childhood wheezing illnesses. Methods: Prospective study of 133 previously healthy infants enrolled during a healthcare visit for a LRTI and followed longitudinally for childhood wheezing illnesses. Urine levels of CC16 at the time of enrollment were measured after validating a commercially available enzyme-linked immunosorbent assay kit for serum. The outcome of interest was parental report of subsequent childhood wheeze (defined as ‡1 episode of wheezing following the initial LRTI) at the 1-year follow-up visit. Logistic regression was used for the main analysis. Results: The median (interquartile range) urine levels of CC16 (ng/mg of creatinine) at the time of an infant LRTI were 11.1 (7.7-20.1) for infants with subsequent childhood wheeze and 13.4 (8.3-61.1) for those without ( p = 0.11). In the main multivariate analysis using a logarithmic transformation of the urine levels of CC16, a twofold increase in urine levels of CC16 was associated with *30% decreased odds (OR = 0.74 [95% confidence interval (CI) 0.56-0.98], p = 0.04) of subsequent childhood wheeze after adjustment for potential confounders. Conclusions: An inverse association was found between urine levels of CC16 at the time of an infant LRTI and the odds of subsequent childhood wheeze. Urine CC16 may be a useful biomarker of the development of childhood wheezing illnesses after LRTIs in infancy.

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“…In cultures of primary human bronchial epithelial cells isolated from enzymatic digests of segments of bronchial tubes from patients with a history of smoking and mild chronic obstructive pulmonary disease undergoing lobectomy for lung cancer, Godding et al (25) reported 15 times lower SC release. Because decreased Clara cell protein (CC10) levels have been measured in epithelial cells from smokers (26), it is possible that synthesis of other proteins such as SC may be similarly altered. Alternatively, the explanation may lay in the different culture conditions.…”

Section: Discussionmentioning

confidence: 99%

IL-8 Released Constitutively by Primary Bronchial Epithelial Cells in Culture Forms an Inactive Complex with Secretory Component

Marshall

Perks

Ferkol

et al. 2001

The Journal of Immunology

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The bronchial epithelium is a source of both α and β chemokines and, uniquely, of secretory component (SC), the extracellular ligand-binding domain of the polymeric IgA receptor. Ig superfamily relatives of SC, such as IgG and α2-macroglobulin, bind IL-8. Therefore, we tested the hypothesis that SC binds IL-8, modifying its activity as a neutrophil chemoattractant. Primary bronchial epithelial cells were cultured under conditions to optimize SC synthesis. The chemokines IL-8, epithelial neutrophil-activating peptide-78, growth-related oncogene α, and RANTES were released constitutively by epithelial cells from both normal and asthmatic donors and detected in high m.w. complexes with SC. There were no qualitative differences in the production of SC-chemokine complexes by epithelial cells from normal or asthmatic donors, and in all cases this was the only form of chemokine detected. SC contains 15% N-linked carbohydrate, and complete deglycosylation with peptide N-glycosidase F abolished IL-8 binding. In micro-Boyden chamber assays, no IL-8-dependent neutrophil chemotactic responses to epithelial culture supernatants could be demonstrated. SC dose-dependently (IC50 ∼0.3 nM) inhibited the neutrophil chemotactic response to rIL-8 (10 nM) in micro-Boyden chamber assays and also inhibited IL-8-mediated neutrophil transendothelial migration. SC inhibited the binding of IL-8 to nonspecific binding sites on polycarbonate filters and endothelial cell monolayers, and therefore the formation of haptotactic gradients, without effects on IL-8 binding to specific receptors on neutrophils. The data indicate that in the airways IL-8 may be solubilized and inactivated by binding to SC.

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Serum and BAL Clara cell 10 kDa protein (CC10) levels and CC10-positive bronchiolar cells are decreased in smokers

Cited by 145 publications

References 33 publications

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

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

Urine Club Cell 16-kDa Secretory Protein and Childhood Wheezing Illnesses After Lower Respiratory Tract Infections in Infancy

IL-8 Released Constitutively by Primary Bronchial Epithelial Cells in Culture Forms an Inactive Complex with Secretory Component

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