Proceedings of The Physiological Society
University of Bristol (2005) J Physiol 567P, C70
Collagenase expressing mast cells accumulate in the walls of peripheral pulmonary arteries at the beginning of hypoxic pulmonary hypertension
Herget, Jan; Vajner, Ludek; Hampl, Vaclav;
1. Physiology, 2nd Medical School, Charles Univ., Prague, Czech Republic. 2. Histology and Embryology, 2nd Medical School, Charles Univ., Prague, Czech Republic.
Chronic hypoxia results in pulmonary hypertension due to vasoconstriction and structural remodelling of peripheral lung blood vessels. We hypothesize that vascular remodelling is initiated in the walls of prealveolar pulmonary arteries by collagenolytic metalloproteinases (MMP) released from activated mast cells. Distribution of mast cells and their expression of interstitial collagenase, MMP-13, in lung conduit, small muscular, and prealveolar arteries was determined quantitatively in lungs of adult male rats exposed for 4 and 20 days to hypoxia (10% 02). Mast cells were identified using Toluidine Blue staining, and MMP-13 expression was detected using monoclonal antibody. Animals were humanely killed at the end of the experiment. After 4, but not after 20 days of hypoxia, a significant (ANOVA) increase in the number of mast cells and their MMP-13 expression was found within walls of prealveolar arteries. In rats with fully developed pulmonary hypertension after 20 days of hypoxia MMP-13 positive mast cells accumulated within the walls of conduit arteries and total number of mast cells was significantly higher than after 4 days exposure and in normoxic controls. These data support the hypothesis that perivascular pulmonary mast cells contribute to the vascular remodeling in hypoxic pulmonary hypertension by releasing interstitial collagenase.
Where applicable, experiments conform with Society ethical requirements