Medicine of the Future in America

Histologic Changes of Doxycycline Pleurodesis in Rabbits: Discussion

Histologic Changes of Doxycycline Pleurodesis in Rabbits: DiscussionAlthough the role of TCNs in enhancing intrapleural coagulation or in depressing fibrinolysis is not known, damage to the surface mesothelium may be important. These cells facilitate fibrinolysis, perhaps through production of a plasminogen activator. If fibrinolysis does not occur, the subsequent stages of injury include a cellular response dominated by fibroblasts and macrophages. Over time, collagen becomes an increasingly substantial component of the pleural stroma. The deposition of collagen is a key stage in pleural fibrosis, representing a longer-lasting matrix component than fibrin canadian drug mall.

There are many possible sources of collagen in the inflamed pleura, including mesothelial cells and fibroblasts. Recently, Antony et al showed that cultured mesothelial cells synthesize a fibroblast-growth-like factor when exposed to TCN. The deposition of collagen might be further enhanced by inhibition of proteolytic mechanisms in the pleural space. We have previously shown that human pleural fluid contains high concentrations of matrix met-alloproteinases, MMP 2 and MMP 9. These enzymes are inhibited by both TCN and DOXY, both in vitro and in vivo.

As these enzymes are more active against denatured collagen (ie, gelatin) than against either interstitial or basement membrane collagen, their role in maintaining pleural integrity and the effect of their inhibition by TCN in promoting pleurodesis is not clear. Perhaps denatured collagen is laid down during fibrin and collagen deposition, analogous to the provisional gel described by Dvorak. If so, then TCNs could work by permitting denatured collagen to deposit on the fibrin and collagen skeleton which, in turn, might facilitate more interstitial collagen to be laid down by fibroblasts.

This entry was posted in Pulmonary function and tagged doxycycline, fibrin collagen, pleural space, pleurodesis.
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