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

Academic Article

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.
  • Authors

    Published In

  • PLoS ONE  Journal
  • Keywords

  • Animals, Calcium, Cell Line, Escherichia coli, Humans, Immunity, Innate, Leukocyte Elastase, Lipopolysaccharides, Macrophages, Alveolar, Matrix Metalloproteinase 9, Mice, Phagocytosis, Protein Binding, Proteolysis, Pulmonary Surfactant-Associated Protein D
  • Digital Object Identifier (doi)

    Pubmed Id

  • 17671221
  • Author List

  • Bratcher PE; Weathington NM; Nick HJ; Jackson PL; Snelgrove RJ; Gaggar A
  • Start Page

  • e41881
  • Volume

  • 7
  • Issue

  • 7