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Cyclic adenosine monophosphate levels and the function of skin microvascular endothelial cells
Author(s) -
Tuder Rubin M.,
Karasek Marvin A.,
Bensch Klaus G.
Publication year - 1990
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041420209
Subject(s) - microbiology and biotechnology , cyclic adenosine monophosphate , biology , adenosine , second messenger system , endothelial stem cell , in vitro , intracellular , chemistry , endocrinology , medicine , biochemistry , receptor
The maintenance of the normal epithelioid morphology of human dermal microvascular endothelial cells (MEC) grown in vitro depends strongly on the presence of factors that increase intracellular levels of cyclic AMP. Complete removal of dibutyryl cAMP and isobutylmethyixanthine (IMX) from the growth medium results in a progressive transition from an epithelioid to a spindle‐shaped cell line. This transition cannot be reversed by the readdition of dibutyryl cAMP and IMX to the growth medium or by addition of agonists that increase cAMP levels. Spindle‐shaped MEC lose the ability to express Factor VIII rAG and DR antigens and to bind peripheral blood mononuclear leukocyte (PBML). Ultrastructural analyses of transitional cells and spindle‐shaped cells show decreased numbers of Weibel‐Palade bodies in transitional cells and their complete absence in spindle‐shaped cells. Interferon‐γ alters several functional properties of both epitheliod and spindle‐shaped cells. In the absence of dibutyryl cAMP it accelerates the transition from epithelial to spindle‐shaped cells, whereas in the presence of cyclic AMP interferon‐γ increases the binding of PBMLs to both epithelioid and spindle‐shaped MEC and the endocytic activity of the endothelial cells. These results suggest that cyclic AMP is an important second messenger in the maintenance of several key functions of microvascular endothelial cells. Factors that influence the levels of this messenger in vivo can be expected to influence the angiogenic and immunologic functions of the microvasculature.