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PloS one2014; 9(4); e96217; doi: 10.1371/journal.pone.0096217

Secretoglobin 1A1 and 1A1A differentially regulate neutrophil reactive oxygen species production, phagocytosis and extracellular trap formation.

Abstract: 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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Publication Date: 2014-04-28 PubMed ID: 24777050PubMed Central: PMC4002474DOI: 10.1371/journal.pone.0096217Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research examines the role of two proteins, Secretoglobin 1A1 and 1A1A, in regulating the production of reactive oxygen species, phagocytosis, and neutrophil extracellular trap (NET) formation in case of lung diseases. The study found disparities in the relative abundance of these proteins in lung secretions, suggesting that these differences contribute to the progression of lung diseases characterized by neutrophilic inflammation, like equine recurrent airway obstruction and asthma.

Examining Secretoglobin Variants

  • The researchers looked at Secretoglobin family 1A member 1 (SCGB 1A1), a small protein majorly secreted by mucosal epithelial cells in lungs and uterus, which is associated with anti-inflammatory properties.
  • SCGB 1A1’s concentration has been found to be reduced in cases of equine recurrent airway obstruction (RAO) and human asthma.
  • Through this study, the researchers explored the direct effects of SCGB 1A1 on neutrophil functions (neutrophils being a type of white blood cell responsible for immune responses).
  • The researchers detected that SCGB1A1 gene is triplicated in equids, producing two distinct proteins: SCGB 1A1 and 1A1A.

Experiment and Findings

  • Through this study, both forms of the proteins (SCGB 1A1 and 1A1A) were produced as recombinant proteins and their effects on certain neutrophil functions, including reactive oxygen species production, phagocytosis, chemotaxis, and neutrophil extracellular trap (NET) formation were tested.
  • Findings revealed that SCGB 1A1A influence increased neutrophil oxidative burst and phagocytosis, while both SCGB 1A1 and 1A1A significantly reduced chemotaxis, with SCGB 1A1A reducing it more.
  • NET formation was seen to be reduced by both SCGB 1A1 and 1A1A in a time- and concentration-dependent manner.
  • It was found that horses with RAO had lower concentrations of SCGB in their bronchial biopsies and bronchoalveolar lavage fluid, while NETs were present in fluid from horses with exacerbated RAO but not in those where RAO was in remission or healthy horses.

Implications

  • The study deduces that SCGB 1A1 and 1A1A have both overlapping and diverging functions.
  • The differences in the relative abundance of these proteins in airway secretions in animals with RAO prompt the understanding that these functional disparities might contribute to the pathogenesis of RAO and other lung diseases characterized by neutrophilic inflammation.
  • Understanding the function of these proteins and their impact on the immune response could provide critical insights into potential therapeutic strategies for related lung diseases.

Cite This Article

APA
Côté O, Clark ME, Viel L, Labbé G, Seah SY, Khan MA, Douda DN, Palaniyar N, Bienzle D. (2014). Secretoglobin 1A1 and 1A1A differentially regulate neutrophil reactive oxygen species production, phagocytosis and extracellular trap formation. PLoS One, 9(4), e96217. https://doi.org/10.1371/journal.pone.0096217

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 9
Issue: 4
Pages: e96217
PII: e96217

Researcher Affiliations

Côté, Olivier
  • Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada.
Clark, Mary Ellen
  • Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada.
Viel, Laurent
  • Department of Clinical Studies, University of Guelph, Guelph, Ontario, Canada.
Labbé, Geneviève
  • Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada.
Seah, Stephen Y K
  • Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada.
Khan, Meraj A
  • Program in Physiology and Experimental Medicine, Lung Innate Immunity Research Laboratory, Hospital for Sick Children, Toronto, Ontario, Canada.
Douda, David N
  • Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Program in Physiology and Experimental Medicine, Lung Innate Immunity Research Laboratory, Hospital for Sick Children, Toronto, Ontario, Canada.
Palaniyar, Nades
  • Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Program in Physiology and Experimental Medicine, Lung Innate Immunity Research Laboratory, Hospital for Sick Children, Toronto, Ontario, Canada.
Bienzle, Dorothee
  • Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada.

MeSH Terms

  • Airway Obstruction / genetics
  • Airway Obstruction / metabolism
  • Animals
  • Base Sequence
  • Bronchoalveolar Lavage Fluid / chemistry
  • Chemotaxis / drug effects
  • Dose-Response Relationship, Drug
  • Extracellular Traps / drug effects
  • Extracellular Traps / metabolism
  • Horses
  • Humans
  • Interleukin-8 / pharmacology
  • Molecular Sequence Data
  • Neutrophils / cytology
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Phagocytosis / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism
  • Recurrence
  • Respiratory Burst / drug effects
  • Secretoglobins / genetics
  • Secretoglobins / metabolism
  • Secretoglobins / pharmacology
  • Time Factors

Conflict of Interest Statement

Dr Nades Palaniyar is an Academic Editor for PLOS ONE. This does not alter the authors' adherence to PLOS ONE Editorial policies and criteria.

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