Open AccessIn vitro hypoxia increases production of matrix metalloproteinases and tryptase in isolated rat lung mast cells
Author(s) -
Hana Maxová,
Jaovotná,
Luděk Vajner,
H Tomášová,
Richard Vytášek,
M Vízek,
Lucie Bačáková,
Valousková,
T Eliásová,
J Herget
Publication year - 2008
Publication title -
physiological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.647
H-Index - 70
eISSN - 1802-9973
pISSN - 0862-8408
DOI - 10.33549/physiolres.931278
Subject(s) - matrix metalloproteinase , hypoxia (environmental) , tryptase , collagenase , interstitial collagenase , in vitro , western blot , connective tissue , chemistry , lung , elastin , percoll , pathology , biology , microbiology and biotechnology , mast cell , immunology , medicine , biochemistry , enzyme , organic chemistry , oxygen , gene
Chronic hypoxia results in hypoxic pulmonary hypertension characterized by fibrotization and muscularization of the walls of peripheral pulmonary arteries. This vessel remodeling is accompanied by an increase in the amount of lung mast cells (LMC) and the presence of small collagen cleavage products in the vessel walls. We hypothesize that hypoxia activates LMC, which release matrix metalloproteinases (MMPs) cleaving collagen and starting increased turnover of connective tissue proteins. This study was designed to determine whether in vitro hypoxia stimulates production of MMPs in rat LMC and increases their collagenolytic activity. The LMC were separated on the Percoll gradient and then were divided into two groups and cultivated for 24 h in 21 % O(2) + 5 % CO(2) or in 10 % O(2) + 5 % CO(2). Presence of the rat interstitial tissue collagenase (MMP-13) in LMC was visualized by immunohistological staining and confirmed by Western blot analysis. Total MMPs activity and tryptase activity were measured in both cultivation media and cellular extracts. Exposure to hypoxia in vitro increased the amount of cells positively labeled by anti-MMP-13 antibody as well as activities of all measured enzymes. The results therefore support the concept that LMC are an important source of increased collagenolytic activity in chronic hypoxia.