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Open Access Research article

The new anti-actin agent dihydrohalichondramide reveals fenestrae-forming centers in hepatic endothelial cells

Filip Braet1*, Ilan Spector2, Nava Shochet2, Phillip Crews3, Tatsuo Higa4, Eline Menu5, Ronald de Zanger1 and Eddie Wisse1

Author Affiliations

1 Laboratory for Cell Biology and Histology, Free University of Brussels (VUB), Laarbeeklaan 103, 1090 Brussels-Jette, Belgium

2 Department of Physiology and Biophysics, Health Science Center, State University of New York at Stony Brook (SUNY), Stony Brook, NY 11794-8661, New York, USA

3 Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 9506, USA

4 Department of Marine Sciences, University of the Ryukyus, Nishihara, Okinawa 903-01, Japan

5 Department of Hematology and Immunology, Free University of Brussels (VUB), Laarbeeklaan 103, 1090 Brussels-Jette, Belgium

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BMC Cell Biology 2002, 3:7  doi:10.1186/1471-2121-3-7

Published: 21 March 2002

Abstract

Background

Liver 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.

Results

Halichondramide 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.