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

First published in American Journal of Respiratory and Critical Care Medicine on 2011 Apr.
Am J Respir Crit Care Med. 2011 Apr 1;183(7):856-64. doi: 10.1164/rccm.201004-0654OC.

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

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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