Modulation of cultured pulmonary microvessel and arterial endothelial cell barrier structure and function by serotonin.
Pulmonary microvessel endothelial cell and pulmonary artery endothelial cell monolayers in tissue culture were treated with serotonin (5-hydroxytryptamine; 5-HT) alone or in conjunction with histamine, bradykinin, the thromboxane analog U-46619, and the actin modulating agent cytochalasin B. After agent treatment, cross-sections through endothelial cell (EC) monolayers were examined by light microscopy and the percentage and widths of intercellular openings were quantitated. To correlate structural changes in the endothelial barrier with an alteration in permeability, EC monolayers cultured on micropore filters were assayed for transit of Evan's blue albumin (EBA) following treatment with vasoactive mediators. 5-HT was found to decrease the patency of endothelial junctions by up to 94%, compared to untreated monolayers, and to prevent or reverse the appearance of interendothelial gaps induced by histamine, bradykinin, U-46619, and cytochalasin B. The 5-HT effect was dose and time dependent, with a maximal increase in junctional apposition observed at a concentration of 10(-6) M for 30 min. This response was significantly blocked by the 5-HT antagonists LSD and ketanserin. The formation or reduction of interendothelial gaps by histamine, bradykinin, and U-46619 and by 5-HT, respectively, was positively correlated to changes in monolayer permeability to EBA. These results suggest that pulmonary edema caused by inflammatory mediators in part may be a consequence of transient increases in pulmonary EC junctional gaps, and that 5-HT may contribute to the homeostatic maintenance of endothelial barrier integrity.
Mineau-Hanschke
R
R
Department of Biology, Boston University, Massachusetts 02215.
Wiles
M E
ME
Morel
N
N
Hechtman
H B
HB
Shepro
D
D
D000818:Animals; D001158:Arteries / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects; D046508:Culture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006632:Histamine / Q000494:pharmacology; D007249:Inflammation / Q000503:physiopathology; D008168:Lung / Q000098:blood supply*; D008833:Microcirculation / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D012702:Serotonin Antagonists; D012701:Serotonin; D006632:Histamine; D001920:Bradykinin