Inhibition of tumor necrosis factor alpha-induced vascular endothelial permeability by gadolinium chloride.
Tumor necrosis factor-alpha (TNF alpha) is an important mediator of endotoxic and septic shock. We previously reported that the survival rate in a rat sepsis model was improved by the administration of gadolinium chloride (GdCl3), whereas the level of TNF alpha in the blood was not affected. In the present study, we examined the effect of GdCl3 on endothelial permeability in vitro. Endothelial permeability was monitored by measuring the amount of fluorescein isothiocyanate-labeled dextran (FITC-Dx) passing through the calf pulmonary arterial endothelial (CPAE) cell monolayer. The incubation of the CPAE cell monolayer with TNF alpha (10-500 JUR/ml for 6-24 h) caused a dose- and time-dependent increase in the permeation of FITC-Dx passing through the monolayer. Whereas the integrity of the monolayer was not affected after preincubation with GdCl3 at concentrations from 10(-7) to 10(-4) M, the increased endothelial permeability induced by TNF alpha was inhibited by a pretreatment of the CPAE cell monolayer with GdCl3 in a dose-dependent manner. Our results suggest that GdCl3 has a protective effect on the endothelial cell monolayer exposed to TNF alpha.
Kusama
T
T
First Department of Surgery, Yamanashi Medical University, Japan. kusamat@res.yamanashi-med.ac.jp
Kohno
H
H
Idezawa
T
T
Fujii
H
H
Yamamoto
M
M
Matsumoto
Y
Y
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002417:Cattle; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D005682:Gadolinium / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005682:Gadolinium; C038958:gadolinium chloride