Artikel
SAH-CSF induces endothelial intercellular gap formation via cytosolic Ca2+-oscillations
Liquor von SAB-Patienten induziert endotheliale interzelluläre Lückenbildung durch zytosolische Ca2+-Oszillationen
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Veröffentlicht: | 8. Mai 2006 |
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Objective: Endothelial cells act like an interface between blood and the vessel wall regulating receptor activity, synthesis and release of nitric oxide and regulation of vessel permeability. All these functions are Ca2+-dependent. The aim of this study was to investigate the influence of cisternal CSF from patients after SAH on the endothelial cytosolic Ca2+-concentration and intercellular gap formation.
Methods: In this experimental model, cultured HUVEC (human umbilical cord vein endothelial cells) were incubated with cisternal cerebrospinal fluid from 8 SAH-patients. Four of these patients had cerebral vasospasm. In control experiments native CSF was used. The Ca2+-concentration and intercellular gap formation was recorded by Fura 2-microfluometry.
Results: Incubation of HUVEC with SAH-CSF provoked cytosolic Ca2+ oscillations in 6 of 8 cases. After perfusion with CSF, sampled from patients with vasospasm (n=4), endothelial Ca2+-oscillations appeared immediately in all cases. The mean oscillation frequency was 0,27±0,016 min-1 (mean value±SEM; n=44 cells). In the presence of the endoplasmic reticulum (ER) Ca-ATPase inhibitor tapsigargin the oscillations ceased in all cells. In further experiments the ER inositol-triphosphate (IP3) receptor gated Ca2+-channels were blocked by xestospongin and the ryanodine-dependent Ca2+-channels by rayanidine. Xestospongin lead to a significant reduction of the Ca2+ oscillation-frequency whereas rayanidine had no influence on the frequency. No control experiments with native CSF no oscillations were observed. When Ca2+ oscillation occurred intercellular gaps increased by 79,4±8% within 60 min (mean value±SEM; P=0.007). In no significant change in gap size were observed in experiments with native CSF or SAH-CSF not inducing Ca2+ oscillations.
Conclusions: Cisternal SAH-CSF, especially from patients with cerebral vasospasms, is able to induce endothelial cytosolic Ca2+ oscillations via ER-Ca2+-ATPase and ER-IP3 receptor gated Ca2+-channels. These oscillations lead to increased vessel permeability by intercellular gap formation.