[Molecular mechanism of erythromycin in the improvement of paraquat-damaged vascular endothelial cell barrier function].
OBJECTIVE
To find out the effects of erythromycin in protecting the vascular endothelial cell barrier against paraquat-induced damages and its underlying molecular and cellular mechanisms.


METHODS
Human umbilical vein endothelial cells (HUVEC) was cultured in two compartment spreading apparatus in vitro. The cultured endothelial cells were divided into three groups: control group (N), paraquat group (P), paraquat + erythromycin group (P + E). The cellular permeability, cAMP concentration, F-actin distribution and content in vascular endothelial cells were measured by immunofluorescence and immunoradiometric assay.


RESULTS
Endothelial cell permeability in P group was significantly higher than that of the other two groups (P < 0.01), which was associated with morphological changes, F-actin content elevation (P < 0.05) and the decreased endothelial cAMP concentration (P < 0.05). While cellular permeability in P + E group increased at 24 h, and dropped back at 36 h with cAMP elevation and F-actin redistribution from center to peripherals (P < 0.01). There were all negative correlations between the permeability and cAMP concentration in P group and P + E group (r = -0.913, -0.648, P < 0.05), but positive correlation between the permeability and F-actin content in these two groups (r = 0.921, 0.817, P < 0.05).


CONCLUSIONS
Erythromycin could decrease endothelial cell permeability with intracellular cAMP concentration increased and cytoskeleton stabilized, which might be the possible mechanisms for the protection of vascular endothelial cell barrier function impaired by paraquat.
Du
Yu
Y
Department of Emergency, West China Hospital, Sichuan University, Chengdu 610041, China.
He
Qing
Q
D002463:Cell Membrane Permeability / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D042783:Endothelial Cells / Q000473:pathology / Q000502:physiology*; D004917:Erythromycin / Q000494:pharmacology*; D006801:Humans; D010269:Paraquat / Q000633:toxicity*; D014471:Umbilical Veins / Q000166:cytology
D004917:Erythromycin; D000242:Cyclic AMP; D010269:Paraquat