Clara Cell Secretory Protein Is Reduced in Equine Recurrent Airway Obstruction

Katavolos, Paula; Ackerley, Cameron; Viel, Laurent; Clark, Mary E.; Wen, Xin; Bienzle, Dorothee

doi:10.1354/vp.08-vp-0255-b-fl

Cited by 27 publications

(49 citation statements)

References 34 publications

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“…Previous studies showed that SCGB1A1 was reduced in horses with RAO compared to those without lung disease, but did not assess expression of individual genes [17]. Here, SCGB expression was compared to glyceraldehyde 3-phosphate dehydrogenase ( GAPDH ) mRNA and 18S ribosomal RNA ( RN18S ) as internal controls.…”

Section: Resultsmentioning

confidence: 98%

“…RAO and control horses ranged in age from 6 to 18 years and were selected according to previously established criteria [17]. Clinical challenge, pulmonary function testing (PFT), and BAL procedures were performed as described [17]. Briefly, horses were maintained outdoor to limit dust and mould exposure preceding the study.…”

Section: Methodsmentioning

confidence: 99%

“…Influx of neutrophils into the airways is a hallmark of the condition [16]. Horses with RAO have low levels of SCGB1A1 mRNA in the lungs and low protein concentration in bronchoalveolar lavage (BAL) fluid [17]. The recent discovery that the SCGB1A1 gene is triplicated in the equine genome, and that the copies evolved differently over time, suggested that different gene products may play important roles in natural adaptation, biological advantage, and possible functional divergence in health and disease [18].…”

Section: Introductionmentioning

confidence: 99%

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Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation

et al. 2014

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Secretoglobin family 1A member 1 (SCGB 1A1) is a small protein mainly secreted by mucosal epithelial cells of the lungs and uterus. SCGB 1A1, also known as club (Clara) cell secretory protein, represents a major constituent of airway surface fluid. The protein has anti-inflammatory properties, and its concentration is reduced in equine recurrent airway obstruction (RAO) and human asthma. RAO is characterized by reversible airway obstruction, bronchoconstriction and neutrophilic inflammation. Direct effects of SCGB 1A1 on neutrophil functions are unknown. We have recently identified that the SCGB1A1 gene is triplicated in equids and gives rise to two distinct proteins. In this study we produced the endogenously expressed forms of SCGBs (SCGB 1A1 and 1A1A) as recombinant proteins, and analyzed their effects on reactive oxygen species production, phagocytosis, chemotaxis and neutrophil extracellular trap (NET) formation ex vivo. We further evaluated whether NETs are present in vivo in control and inflamed lungs. Our data show that SCGB 1A1A but not SCGB 1A1 increase neutrophil oxidative burst and phagocytosis; and that both proteins markedly reduce neutrophil chemotaxis. SCGB 1A1A reduced chemotaxis significantly more than SCGB 1A1. NET formation was significantly reduced in a time- and concentration-dependent manner by SCGB 1A1 and 1A1A. SCGB mRNA in bronchial biopsies, and protein concentration in bronchoalveolar lavage fluid, was lower in horses with RAO. NETs were present in bronchoalveolar lavage fluid from horses with exacerbated RAO, but not in fluid from horses with RAO in remission or in challenged healthy horses. These findings indicate that SCGB 1A1 and 1A1A have overlapping and diverging functions. Considering disparities in the relative abundance of SCGB 1A1 and 1A1A in airway secretions of animals with RAO suggests that these functional differences may contribute to the pathogenesis of RAO and other neutrophilic inflammatory lung diseases.

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Section: Resultsmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation

et al. 2014

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“…As to CC10, several previous investigations have demonstrated lower levels in BALF of smokers than nonsmokers [7,11–14], and significantly decreased BALF CC10 levels were also detected in smokers compared with nonsmokers in a recent proteomic study [15]. Moreover, reduced production of CC10 and decreased CC10 levels in BALF appear to be features of environmentally induced lung inflammation in horses [13] and rats [14]. …”

Section: Discussionmentioning

confidence: 94%

Intriguing bronchoalveolar lavage proteome in a case of pulmonary langerhans cell histiocytosis

Ghafouri¹,

Persson

Tagesson

2013

Am J Case Rep

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Background:Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial lung disease associated with tobacco smoke exposure. New insights into its pathogenesis and how it differs from that of chronic obstructive pulmonary disease (COPD) may be provided by proteomic studies on bronchoalveolar lavage fluid (BALF).Case Report:We present the BALF proteome in a biopsy-proven case of PLCH and compare it with typical proteomes of COPD and of the healthy lung. The BALF proteins were separated by two-dimensional gel electrophoresis (2-DE) and the protein patterns were analyzed with a computerized 2-DE imaging system. As compared to the healthy subject and the COPD case, the PLCH case showed a strikingly different 2-DE pattern. There was much more IgG (heavy chain) and orosomucoid, and less α1-antitrypsin, surfactant protein-A, haptoglobin, cystatin-S, Clara cell protein 10, transthyretin and gelsolin. Moreover, no apolipoprotein-A1, pro-apolipoprotein-A1, amyloid P, calgranulin A, or calgranulin B was detected at all.Conclusions:This case of PLCH presents with an extreme BALF proteome lacking significant amounts of protective and anti-inflammatory proteins. Thus, the intriguing BALF proteome opens up new lines of research into the pathophysiology of PLCH and how its pathogenesis differs from that in COPD.

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“…Immunohistochemical analysis has evidenced the presence of cytochrome P450 (Cytochrome Proteins) (CYP) in lung cells such as: macrophages (Pavek & Dvorak, 2008), endothelium, alveolar cells types I and II, ciliated cells (Castell et al, 2005) and Non-Ciliated Bronchiolar Cell or Clara cell. Clara cells are the leading cells for xenobiotic metabolism in the lung because its profuse cytochrome P450 mono oxygenase activity (Katavolos et al, 2009). …”

Section: Lung Metabolic Active Cellsmentioning

confidence: 99%