Editors' ChoiceImaging and Cell Biology

Secret Entry for Dendritic Cells

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Science Translational Medicine  23 Dec 2009:
Vol. 1, Issue 12, pp. 12ec45
DOI: 10.1126/scitranslmed.3000734

The mysterious way in which blood cells waft throughout the interstitial space appears to be an open unidirectional form of communication with the lymphatic system. Guidance cues for migration are expressed by the lymphatic endothelium and sensed by blood cells, allowing cell movement to rely less on physical integrin posts and more on the plasticity of the cell body to propel through three-dimensional environments. Such is not the case when blood cells penetrate stiff barriers such as basement membranes, in which well-controlled molecular interactions are thought to be required for entry through cell-cell junctional seals. Using in situ live-cell imaging of mouse dermis, Pflicke and Sixt show that dendritic cells, large antigen-presenting cells found in the blood, can migrate through the basement membrane into the lymphatic system without the need for cell-matrix interactions. Two patterns of migration were observed: a slow approach to the basement membrane, followed by acceleration or straight migration of the dendritic cell into the lymphatic lumen. The reason for this easy passage, as they show with immunohistology and immunoelectronmicroscopy, is that lymphatic basement membranes have fragile areas that are perforated and completely devoid of essential basement membrane components. Live cell images revealed that these perforations serve as secret penetration points for approaching dendritic cells, independent of any physical adhesion molecules or biochemical remodeling. As dendritic cells pass through, hydrostatic pressure controls the expansion and retraction of the basement membrane perforations, altering our view of this structure as a sheet-like barrier. Instead, these findings suggest that the basement membrane is a more dynamic, three-dimensional scaffold and emphasize the fluidity of cellular communication.

H. Pflicke et al., Preformed portals facilitate dendritic cell entry into afferent lymphatic vessels. J. Exp. Med. 7 December 2009 (10.1084/jem.20091739). [Abstract]

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