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MMP-9 cleaves SP-D and abrogates its innate immune functions in vitro

Bratcher, PE and Weathington, NM and Nick, HJ and Jackson, PL and Snelgrove, RJ and Gaggar, A (2012) MMP-9 cleaves SP-D and abrogates its innate immune functions in vitro. PLoS ONE, 7 (7).

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Abstract

Possession of a properly functioning innate immune system in the lung is vital to prevent infections due to the ongoing exposure of the lung to pathogens. While mechanisms of pulmonary innate immunity have been well studied, our knowledge of how these systems are altered in disease states, leading to increased susceptibility to infections, is limited. One innate immune protein in the lung, the pulmonary collectin SP-D, has been shown to be important in innate immune defense, as well as clearance of allergens and apoptotic cells. MMP-9 is a protease with a wide variety of substrates, and has been found to be dysregulated in a myriad of lung diseases ranging from asthma to cystic fibrosis; in many of these conditions, there are decreased levels of SP-D. Our results indicate that MMP-9 is able to cleave SP-D in vitro and this cleavage leads to loss of its innate immune functions, including its abilities to aggregate bacteria and increase phagocytosis by mouse alveolar macrophages. However, MMP-9-cleaved SP-D was still detected in a solid-phase E. coli LPS-binding assay, while NE-cleaved SP-D was not. In addition, MMP-9 seems to cleave SP-D much more efficiently than NE at physiological levels of calcium. Previous studies have shown that in several diseases, including cystic fibrosis and asthma, patients have increased expression of MMP-9 in the lungs as well as decreased levels of intact SP-D. As patients suffering from many of the diseases in which MMP-9 is over-expressed can be more susceptible to pulmonary infections, it is possible that MMP-9 cleavage of SP-D may contribute to this phenotype.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Bratcher, PE
Weathington, NMWeathington@pitt.eduNMW37
Nick, HJ
Jackson, PL
Snelgrove, RJ
Gaggar, A
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorBenarafa, CharafUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 30 July 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 7
DOI or Unique Handle: 10.1371/journal.pone.0041881
Schools and Programs: School of Medicine > Medicine
Refereed: Yes
Other ID: NLM PMC3408449
PubMed Central ID: PMC3408449
PubMed ID: 22860023
Date Deposited: 29 Oct 2012 15:27
Last Modified: 30 Oct 2018 13:57
URI: http://d-scholarship.pitt.edu/id/eprint/15602

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