Segmental allergen challenge alters multimeric structure and function of surfactant protein D in humans

Elena N. Atochina-Vasserman, Carla Winkler, Helen Abramova, Frank Schaumann, Norbert Krug, Andrew J. Gow, Michael F. Beers, Jens M. Hohlfeld

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Rationale: Surfactant protein D (SP-D), a 43-kD collectin, is synthesized and secreted by airway epithelia as a dodecamer formed by assembly of four trimeric subunits. We have previously shown that the quaternary structure of SP-D can be altered during inflammatory lung injury through its modification by S-nitrosylation, which in turn alters its functional behavior producing a proinflammatory response in effector cells. Objectives: We hypothesized that alterations in structure and function of SP-D may occur in humans with acute allergic inflammation. Methods: Bronchoalveolar lavage (BAL) fluid was collected from 15 nonsmoking patients with mild intermittent allergic asthma before and 24 hours after segmental provocation with saline, allergen, LPS, and mixtures of allergen and LPS. Structural modifications of SP-D were analyzed by native and sodium dodecyl sulfate gel electrophoresis. Measurements and Main Results: The multimeric structure of native SP-D was found to be disrupted after provocation with allergen or a mixture of allergen and LPS. Interestingly, under reducing conditions, sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that 7 of 15 patients with asthma developed an abnormal cross-linked SP-D band after segmental challenge with either allergen or a mixture of allergen with LPS but not LPS alone. Importantly, patients with asthma with cross-linked SP-D demonstrated significantly higher levels of BAL eosinophils, nitrogen oxides, IL-4, IL-5, IL-13, and S-nitrosothiol-SP-D compared with patients without cross-linked SP-D. Conclusions:We conclude that segmental allergen challenge results in changes of SP-D multimeric structure and that these modifications are associated with an altered local inflammatory response in the distal airways.

Original languageEnglish
Pages (from-to)856-864
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume183
Issue number7
DOIs
Publication statusPublished - 1 Apr 2011
Externally publishedYes

Fingerprint

Pulmonary Surfactant-Associated Protein D
Allergens
Asthma
Sodium Dodecyl Sulfate
S-Nitrosothiols
Nitrogen Oxides
Interleukin-13
Interleukin-5
Bronchoalveolar Lavage Fluid
Lung Injury
Bronchoalveolar Lavage
Eosinophils
Interleukin-4
Electrophoresis
Polyacrylamide Gel Electrophoresis
Epithelium
Gels

Keywords

  • Biomarker
  • Human asthma
  • Nitric oxide
  • Pulmonary collectins
  • Surfactant proteins

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Segmental allergen challenge alters multimeric structure and function of surfactant protein D in humans. / Atochina-Vasserman, Elena N.; Winkler, Carla; Abramova, Helen; Schaumann, Frank; Krug, Norbert; Gow, Andrew J.; Beers, Michael F.; Hohlfeld, Jens M.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 183, No. 7, 01.04.2011, p. 856-864.

Research output: Contribution to journalArticle

Atochina-Vasserman, Elena N. ; Winkler, Carla ; Abramova, Helen ; Schaumann, Frank ; Krug, Norbert ; Gow, Andrew J. ; Beers, Michael F. ; Hohlfeld, Jens M. / Segmental allergen challenge alters multimeric structure and function of surfactant protein D in humans. In: American Journal of Respiratory and Critical Care Medicine. 2011 ; Vol. 183, No. 7. pp. 856-864.
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abstract = "Rationale: Surfactant protein D (SP-D), a 43-kD collectin, is synthesized and secreted by airway epithelia as a dodecamer formed by assembly of four trimeric subunits. We have previously shown that the quaternary structure of SP-D can be altered during inflammatory lung injury through its modification by S-nitrosylation, which in turn alters its functional behavior producing a proinflammatory response in effector cells. Objectives: We hypothesized that alterations in structure and function of SP-D may occur in humans with acute allergic inflammation. Methods: Bronchoalveolar lavage (BAL) fluid was collected from 15 nonsmoking patients with mild intermittent allergic asthma before and 24 hours after segmental provocation with saline, allergen, LPS, and mixtures of allergen and LPS. Structural modifications of SP-D were analyzed by native and sodium dodecyl sulfate gel electrophoresis. Measurements and Main Results: The multimeric structure of native SP-D was found to be disrupted after provocation with allergen or a mixture of allergen and LPS. Interestingly, under reducing conditions, sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that 7 of 15 patients with asthma developed an abnormal cross-linked SP-D band after segmental challenge with either allergen or a mixture of allergen with LPS but not LPS alone. Importantly, patients with asthma with cross-linked SP-D demonstrated significantly higher levels of BAL eosinophils, nitrogen oxides, IL-4, IL-5, IL-13, and S-nitrosothiol-SP-D compared with patients without cross-linked SP-D. Conclusions:We conclude that segmental allergen challenge results in changes of SP-D multimeric structure and that these modifications are associated with an altered local inflammatory response in the distal airways.",
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AU - Atochina-Vasserman, Elena N.

AU - Winkler, Carla

AU - Abramova, Helen

AU - Schaumann, Frank

AU - Krug, Norbert

AU - Gow, Andrew J.

AU - Beers, Michael F.

AU - Hohlfeld, Jens M.

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AB - Rationale: Surfactant protein D (SP-D), a 43-kD collectin, is synthesized and secreted by airway epithelia as a dodecamer formed by assembly of four trimeric subunits. We have previously shown that the quaternary structure of SP-D can be altered during inflammatory lung injury through its modification by S-nitrosylation, which in turn alters its functional behavior producing a proinflammatory response in effector cells. Objectives: We hypothesized that alterations in structure and function of SP-D may occur in humans with acute allergic inflammation. Methods: Bronchoalveolar lavage (BAL) fluid was collected from 15 nonsmoking patients with mild intermittent allergic asthma before and 24 hours after segmental provocation with saline, allergen, LPS, and mixtures of allergen and LPS. Structural modifications of SP-D were analyzed by native and sodium dodecyl sulfate gel electrophoresis. Measurements and Main Results: The multimeric structure of native SP-D was found to be disrupted after provocation with allergen or a mixture of allergen and LPS. Interestingly, under reducing conditions, sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that 7 of 15 patients with asthma developed an abnormal cross-linked SP-D band after segmental challenge with either allergen or a mixture of allergen with LPS but not LPS alone. Importantly, patients with asthma with cross-linked SP-D demonstrated significantly higher levels of BAL eosinophils, nitrogen oxides, IL-4, IL-5, IL-13, and S-nitrosothiol-SP-D compared with patients without cross-linked SP-D. Conclusions:We conclude that segmental allergen challenge results in changes of SP-D multimeric structure and that these modifications are associated with an altered local inflammatory response in the distal airways.

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KW - Pulmonary collectins

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