Journal
MICROVASCULAR RESEARCH
Volume 76, Issue 1, Pages 46-51Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mvr.2008.02.003
Keywords
permeability; lymphatic endothelial cells; cAMP; barrier function; microvascular tissue engineering
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Funding
- NIBIB NIH HHS [R21 EB002228-02, R21 EB002228, EB002228, EB005792, R01 EB005792, R01 EB005792-03] Funding Source: Medline
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This work examines the effect of cyclic AMP (cAMP) on the in vitro barrier function of tubes of human dermal lymphatic microvascular endothelial cells (LECs). Under baseline conditions, the barrier function of LEC tubes was weak, with diffusional permeability coefficients to bovine serum albumin and 10 kDa dextran of 1.4(-0.6)(+0.9) x 10(-6) cm/s and 1.7(-0.5)(+0.8) x 10(-6) cm/s (geometric mean +/- 95% CI), respectively, and 1.2 +/- 0.5 (mean 95% CI) focal leaks per mm. Exposure to low concentrations (3 mu M) of a cell-permeant analog of cAMP did not alter the barrier function. Exposure to higher concentrations (80 and 400 mu M) and/or the phosphodiesterase inhibitor Ro-20-1724 (20 mu M) lowered permeabilities and the number of focal leaks, and increased the selectivity of the barrier. Decreased permeabilities were accompanied by an increase in continuous VE-cadherin staining at cell-cell borders. Exposure to I mM 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, did not increase permeabilities. LECs expressed the lymphatic-specific master transcription factor Prox-1, regardless of whether barrier function was weak or strong. Our results indicate that the permeability of LEC tubes in vitro responds to cAMP in a manner similar to that well-described for the permeability of blood microvessels. (c) 2008 Elsevier Inc. All rights reserved.
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