Abstract
BackgroundLiver sinusoidal endothelial cells (LSECs) react to different anti-actin agents by increasing their number of fenestrae. A new structure related to fenestrae formation could be observed when LSECs were treated with misakinolide. In this study, we investigated the effects of two new actin-binding agents on fenestrae dynamics. High-resolution microscopy, including immunocytochemistry and a combination of fluorescence- and scanning electron microscopy was applied.ResultsHalichondramide and dihydrohalichondramide disrupt microfilaments within 10 minutes and double the number of fenestrae in 30 minutes. Dihydrohalichondramide induces fenestrae-forming centers, whereas halichondramide only revealed fenestrae-forming centers without attached rows of fenestrae with increasing diameter. Correlative microscopy showed the absence of actin filaments (F-actin) in sieve plates and fenestrae-forming centers. Comparable experiments on umbilical vein endothelial cells and bone marrow sinusoidal endothelial cells revealed cell contraction without the appearance of fenestrae or fenestrae-forming centers.Conclusion(I) A comparison of all anti-actin agents tested so far, revealed that the only activity that misakinolide and dihydrohalichondramide have in common is their barbed end capping activity; (II) this activity seems to slow down the process of fenestrae formation to such extent that it becomes possible to resolve fenestrae-forming centers; (III) fenestrae formation resulting from microfilament disruption is probably unique to LSECs.
Highlights
Liver sinusoidal endothelial cells (LSECs) react to different anti-actin agents by increasing their number of fenestrae
Conclusion: (I) A comparison of all anti-actin agents tested so far, revealed that the only activity that misakinolide and dihydrohalichondramide have in common is their barbed end capping activity; (II) this activity seems to slow down the process of fenestrae formation to such extent that it becomes possible to resolve fenestrae-forming centers; (III) fenestrae formation resulting from microfilament disruption is probably unique to LSECs
We report here that HALI and di-h-HALI: (I) disrupts actin organization in LSECs in a distinctive manner; (II) significantly increase the number of fenestrae; (III) that di-hHALI elicits fenestrae-forming centers (FFCs) from which nascent fenestrae are fanning out; and (IV) for reasons of comparison, we examined the effect of HALI and dih-HALI on cultured human umbilical vein endothelial cells (HUVECs) and bone marrow sinusoidal endothelial cells (BECs STR-4)
Summary
Liver sinusoidal endothelial cells (LSECs) react to different anti-actin agents by increasing their number of fenestrae. Liver sinusoidal endothelial cells (LSECs) differ from other endothelial cells They possess open fenestrae that are grouped in sieve plates and lack a basal lamina [1]. Numerous publications appeared about the role of these dynamic structures under various physiological and pathological situations [5] Their role and involvement in the regenerating liver after partial hepatectomy [6], shear stress [7], liposome-mediated transport [8], liver cancer [9], injury by free radicals [10] and chronic alcohol abuse [11], resulting in alcoholismassociated hyperlipoproteinemia [12] have been explored
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