Surfactant protein A increases matrix metalloproteinase-9 production by THP-1 cells

Luis G. Vazquez de Lara, Todd M. Umstead, Sara E. Davis, David S. Phelps

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Matrix metalloproteinase (MMP)-9 from alveolar macrophages is a major source of elastolytic activity in the lung. It is increased in the bronchoalveolar lavage fluid of patients with emphysema. Although the importance of macrophage-derived elastolytic activity in the pathogenesis of emphysema is well established, questions remain about MMP-9 regulation and activity. Because surfactant protein A (SP-A) is capable of modulating other functions of human monocytic cells, we hypothesized that SP-A may regulate MMP-9 expression. Vitamin D3-differentiated THP-1 cells and peripheral blood mononuclear cells were stimulated in vitro with several concentrations of SP-A for different incubation times. MMP-9 mRNA expression was measured by dot-blot analysis, gelatinolytic activity in the medium was determined by gel zymography, protein expression was determined by ELISA, and a specific MMP-9 activity assay was used to measure the state of activation of this enzyme in the cell supernatants. SP-A induced the expression of MMP-9 in both cell types, the effect was time and dose dependent, and MMP-9 was released in its zymogen form. On the basis of results of neutralizing antibody studies, we believe that SP-A action is mediated through Toll-like receptor-2. Even though the biological meaning of these findings remains to be elucidated, these observations suggest the presence of a novel, locally controlled mechanism by which MMP-9 levels may be regulated in alveolar macrophages. We speculate that SP-A may influence the protease/antiprotease balance in the lungs of patients with quantitative and/or qualitative changes in surfactant constituents favoring an abnormal breakdown of extracellular matrix components.

Original languageEnglish (US)
Pages (from-to)L899-L906
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume285
Issue number4 29-4
StatePublished - Oct 1 2003

Fingerprint

Pulmonary Surfactant-Associated Protein A
Matrix Metalloproteinase 9
Emphysema
Alveolar Macrophages
Toll-Like Receptor 2
Lung
Enzyme Precursors
Enzyme Activation
Cholecalciferol
Bronchoalveolar Lavage Fluid
Neutralizing Antibodies
Protease Inhibitors
Surface-Active Agents
Extracellular Matrix
Blood Cells
Peptide Hydrolases
Gels
Enzyme-Linked Immunosorbent Assay
Macrophages
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

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abstract = "Matrix metalloproteinase (MMP)-9 from alveolar macrophages is a major source of elastolytic activity in the lung. It is increased in the bronchoalveolar lavage fluid of patients with emphysema. Although the importance of macrophage-derived elastolytic activity in the pathogenesis of emphysema is well established, questions remain about MMP-9 regulation and activity. Because surfactant protein A (SP-A) is capable of modulating other functions of human monocytic cells, we hypothesized that SP-A may regulate MMP-9 expression. Vitamin D3-differentiated THP-1 cells and peripheral blood mononuclear cells were stimulated in vitro with several concentrations of SP-A for different incubation times. MMP-9 mRNA expression was measured by dot-blot analysis, gelatinolytic activity in the medium was determined by gel zymography, protein expression was determined by ELISA, and a specific MMP-9 activity assay was used to measure the state of activation of this enzyme in the cell supernatants. SP-A induced the expression of MMP-9 in both cell types, the effect was time and dose dependent, and MMP-9 was released in its zymogen form. On the basis of results of neutralizing antibody studies, we believe that SP-A action is mediated through Toll-like receptor-2. Even though the biological meaning of these findings remains to be elucidated, these observations suggest the presence of a novel, locally controlled mechanism by which MMP-9 levels may be regulated in alveolar macrophages. We speculate that SP-A may influence the protease/antiprotease balance in the lungs of patients with quantitative and/or qualitative changes in surfactant constituents favoring an abnormal breakdown of extracellular matrix components.",
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Surfactant protein A increases matrix metalloproteinase-9 production by THP-1 cells. / Vazquez de Lara, Luis G.; Umstead, Todd M.; Davis, Sara E.; Phelps, David S.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 285, No. 4 29-4, 01.10.2003, p. L899-L906.

Research output: Contribution to journalArticle

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