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closeReferee comments: Referee 2
Posted by PLOS_ONE_Group on 25 Feb 2008 at 13:27 GMT
Referee 2's review:
In this manuscript by Phillipson and coworkers, evidence is provided to demonstrate a restructuring of endothelial cells in response to transmigrating neutrophils that serves to minimize plasma protein extravasation across postcapillary venules. These studies add to the growing body of evidence that links neutrophil emigration to vascular permeability and provide novel insights about how endothelial cells respond to inflammatory stimuli in a manner that limits vascular permeability changes and the accompanying edema formation. Overall, the manuscript is well-written and the findings are clearly presented. The authors should consider the following:
1) The finding that adherent neutrophils are encapsulated by endothelial membrane to form an "airlock type seal" during MIP-2 superfusion is reminiscent of work published in the 1980s by Lewis RE and Granger HJ (Microvasc Res. 1988;35:27-47; Microvasc Res. 1989;37:53-69), where similar structural changes by venular endothelial cells were described in hamster cheek pouch venules. The authors should address these early and supportive observations in the manuscript.
2) The authors do not appear to specifically state in the manuscript that MIP-2 induced vascular permeability response in cremaster muscle venules is neutrophil-dependent. It is stated that depletion of neutrophils eliminates leukocyte emigration in this model, but no mention is made of whether albumin leakage is similarly affected. If this information is not available, then one could conclude that the absence of differences in the permeability response between the wild type and Mac-1-/- mice might result from the involvement of a neutrophil-independent mechanisms in the MIP-2 induced albumin leakage.
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N.B. These are the comments made by the referee when reviewing an earlier version of this paper. Prior to publication the manuscript has been revised in light of these comments and to address other editorial requirements.