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

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.

journal_name

Am J Respir Crit Care Med

journal_title

American journal of respiratory and critical care medicine

authors

Atochina-Vasserman EN,Winkler C,Abramova H,Schaumann F,Krug N,Gow AJ,Beers MF,Hohlfeld JM

doi

10.1164/rccm.201004-0654OC

subject

Has Abstract

pub_date

2011-04-01 00:00:00

pages

856-64

issue

eissn

1073-449X

issn

1535-4970

pii

201004-0654OC

journal_volume

183

pub_type

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