Oxidative damage of SP-D abolishes control of eosinophil extracellular DNA trap formation.

Yousefi, Shida; Sharma, Satish K; Stojkov, Darko; Germic, Nina; Aeschlimann, Salome; Ge, Moyar Q; Flayer, Cameron H; Larson, Erik D; Redai, Imre G; Zhang, Suhong; Koziol-White, Cynthia J; Karikó, Katalin; Simon, Hans-Uwe; Haczku, Angela (2018). Oxidative damage of SP-D abolishes control of eosinophil extracellular DNA trap formation. Journal of leukocyte biology, 104(1), pp. 205-214. Society for Leukocyte Biology 10.1002/JLB.3AB1117-455R

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The asthmatic airways are highly susceptible to inflammatory injury by air pollutants such as ozone (O ), characterized by enhanced activation of eosinophilic granulocytes and a failure of immune protective mechanisms. Eosinophil activation during asthma exacerbation contributes to the proinflammatory oxidative stress by high levels of nitric oxide (NO) production and extracellular DNA release. Surfactant protein-D (SP-D), an epithelial cell product of the airways, is a critical immune regulatory molecule with a multimeric structure susceptible to oxidative modifications. Using recombinant proteins and confocal imaging, we demonstrate here that SP-D directly bound to the membrane and inhibited extracellular DNA trap formation by human and murine eosinophils in a concentration and carbohydrate-dependent manner. Combined allergic airway sensitization and O exposure heightened eosinophilia and nos2 mRNA (iNOS) activation in the lung tissue and S-nitrosylation related de-oligomerisation of SP-D in the airways. In vitro reproduction of the iNOS action led to similar effects on SP-D. Importantly, S-nitrosylation abolished the ability of SP-D to block extracellular DNA trap formation. Thus, the homeostatic negative regulatory feedback between SP-D and eosinophils is destroyed by the NO-rich oxidative lung tissue environment in asthma exacerbations.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
09 Interdisciplinary Units > Microscopy Imaging Center MIC

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Yousefi, Shida; Stojkov, Darko; Germic, Nina; Aeschlimann, Salome and Simon, Hans-Uwe

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0741-5400

Publisher:

Society for Leukocyte Biology

Language:

English

Submitter:

Jana Berger

Date Deposited:

04 Jun 2018 10:37

Last Modified:

14 Feb 2019 12:36

Publisher DOI:

10.1002/JLB.3AB1117-455R

PubMed ID:

29733456

Uncontrolled Keywords:

eosinophil extracellular traps (EETs) eosinophils surfactant pulmonary-associated protein D (SP-D)

BORIS DOI:

10.7892/boris.116900

URI:

https://boris.unibe.ch/id/eprint/116900

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