鞘氨醇-1-磷酸通过维持完整微血管内皮表面糖萼来保持正常血管通透性。
Sphingosine-1-phosphate Maintains Normal Vascular Permeability by Preserving Endothelial Surface Glycocalyx in Intact Microvessels.
作者信息
Zhang Lin, Zeng Min, Fan Jie, Tarbell John M, Curry Fitz-Roy E, Fu Bingmei M
机构信息
Department of Biomedical Engineering, The City College of the City University of New York, New York City, New York, USA.
Department of Physiology and Membrane Biology, School of Medicine, University of California at Davis, Davis, California, USA.
出版信息
Microcirculation. 2016 May;23(4):301-10. doi: 10.1111/micc.12278.
OBJECTIVE
S1P was found to protect the ESG by inhibiting MMP activity-dependent shedding of ESG in cultured endothelial cell studies. We aimed to further test that S1P contributes to the maintenance of normal vascular permeability by protecting the ESG in intact microvessels.
METHODS
We quantified the ESG in post-capillary venules of rat mesentery and measured the vascular permeability to albumin in the presence and absence of 1 μM S1P. We also measured permeability to albumin in the presence of MMP inhibitors and compared the measured permeability with those predicted by a transport model for the inter-endothelial cleft.
RESULTS
We found that in the absence of S1P, the fluorescence intensity of the FITC-anti-HS-labeled ESG was ~10% of that in the presence of S1P, whereas the measured permeability to albumin was ~6.5-fold of that in the presence of S1P. Similar results were observed with MMP inhibition. The predictions by the mathematical model further confirmed that S1P maintains microvascular permeability by preserving ESG.
CONCLUSIONS
Our results show that S1P contributes to the maintenance of normal vascular permeability by protecting the ESG in intact microvessels, consistent with parallel observation in cultured endothelial monolayers.
目的
在培养的内皮细胞研究中发现，1-磷酸鞘氨醇（S1P）通过抑制基质金属蛋白酶（MMP）活性依赖性的内皮糖萼（ESG）脱落来保护ESG。我们旨在进一步测试S1P通过保护完整微血管中的ESG来维持正常血管通透性。
方法
我们对大鼠肠系膜毛细血管后微静脉中的ESG进行定量，并在存在和不存在1μM S1P的情况下测量血管对白蛋白的通透性。我们还测量了在MMP抑制剂存在下对白蛋白的通透性，并将测量的通透性与内皮细胞间裂隙转运模型预测的通透性进行比较。
结果
我们发现，在不存在S1P的情况下，异硫氰酸荧光素（FITC）标记抗硫酸乙酰肝素（HS）的ESG荧光强度约为存在S1P时的10%，而测量的白蛋白通透性约为存在S1P时的6.5倍。MMP抑制也观察到类似结果。数学模型的预测进一步证实，S1P通过保留ESG来维持微血管通透性。
结论
我们的结果表明，S1P通过保护完整微血管中的ESG来维持正常血管通透性，这与在培养的内皮细胞单层中的平行观察结果一致。
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