Red blood cells increase secretion of matrix metalloproteinases from human lung fibroblasts in vitro

K. Fredriksson, Xiang-de Liu, J. Lundahl, J. Klominek, S. I. Rennard, C. M. Skold

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Tissue remodeling is an important process in many inflammatory and fibrotic lung disorders. RBC may in these conditions interact with extracellular matrix (ECM). Fibroblasts can produce and secrete matrix components, matrix-degrading enzymes (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Imbalance in matrix synthesis/degradation may result in rearrangement of tissue architecture and lead to diseases such as emphysema or fibrosis. Neutrophil elastase (NE), a protease released by neutrophils, is known to activate MMP. We hypothesized that RBC can stimulate secretion of MMPs from human lung fibroblasts and that NE can augment this effect. Human fetal lung fibroblasts were cultured in floating collagen gels with or without RBC. After 4 days, the culture medium was analyzed with gelatin zymography, Western blot, and ELISA for MMP-1, -2, -3 and TIMP-1, -2. RBC augmented NE-induced fibroblast-mediated collagen gel contraction compared with NE alone (18.4 ± 1.6%, 23.7 ± 1.4% of initial gel area, respectively). A pan-MMP inhibitor (GM-6001) completely abolished the stimulating effect of NE. Gelatin zymography showed that RBC stimulated MMP-2 activity and that NE enhanced conversion to the active form. Addition of GM-6001 completely inhibited MMP-2 activity in controls, whereas it only partially altered RBC-induced MMP activity. Western blot confirmed the presence of MMP-1 and MMP-3 in fibroblasts stimulated with RBC, and ELISA confirmed increased concentrations of pro-MMP-1. We conclude that stimulation of MMP secretion by fibroblasts may explain the ability of RBC to augment fibroblast-mediated collagen gel contraction. This might be a potential mechanism by which hemorrhage in inflammatory conditions leads to ECM remodeling.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume290
Issue number2
DOIs
StatePublished - Feb 1 2006

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Matrix Metalloproteinases
Fibroblasts
Erythrocytes
Leukocyte Elastase
Lung
Gels
Matrix Metalloproteinase Inhibitors
Collagen
Gelatin
Extracellular Matrix
Western Blotting
Enzyme-Linked Immunosorbent Assay
In Vitro Techniques
Tissue Inhibitor of Metalloproteinases
Tissue Inhibitor of Metalloproteinase-2
Tissue Inhibitor of Metalloproteinase-1
Emphysema
Culture Media
Neutrophils
Fibrosis

Keywords

  • Emphysema
  • Erythrocyte
  • Neutrophil elastase
  • Remodeling
  • Tissue inhibitors of metalloproteinases

ASJC Scopus subject areas

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

Cite this

Red blood cells increase secretion of matrix metalloproteinases from human lung fibroblasts in vitro. / Fredriksson, K.; Liu, Xiang-de; Lundahl, J.; Klominek, J.; Rennard, S. I.; Skold, C. M.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 290, No. 2, 01.02.2006.

Research output: Contribution to journalArticle

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