Mast cell activation disrupts interactions between endothelial cells and pericytes during early life allergic asthma
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Abstract
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Together, the need for increased oxygen supply due to tissue expansion and the concurrent reduction in pulmonary vasculature will lead to a quicker deterioration of lung and vascular function overall.
I really like the illustration of what this study found in the graphical abstract. I don't see where the schematic incorporates the hypoxia component. If that is relevant then it may be worth making that clearer.
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during the resolution phase
It would be helpful to the reader to hear more about how the resolution phase was determined.
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Whilst APC-366 did not impact MC degranulation (Fig. 7E-F), pericyte volume was maintained in the presence of the inhibitor (Fig. 7E and G).
I like this last experiment with the specific tryptase inhibitor - and extra plus for doing it in human cells!
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Together these parameters provide an accurate representation of the lung vascular architecture and its impact on inflammation.
It would be interesting to determine which of the 6 different parameters explained most of the variation in lung architecture in case it only takes a couple measurements to assess response to inflammation.
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general protease inhibitor
Can you provide more detail about this general inhibitor? Is this a cocktail? Which mast cell proteases or classes of mast cell proteases (serine, cysteine, etc) would it be predicted to inhibited? Are there mast cell proteases that you believe would still be active in the presence of this inhibitor?
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We utilised fluorescent avidin staining to analyse in detail the profile of degranulated CTMCs as we and others have demonstrated that it provides an accurate measurement of the localisation and cellular interactions of extracellular CTMC granules
I'm interested in whether you saw a difference in staining between granules that were extracellular to the MCs or the ones associated with changes in pericyte morphology.
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loss of surface N-cadherin
Is the idea that the mast cell proteases are directly cleaving N-cadherin, leading to its loss from the cell surface? Is it a known substrate for mast cell proteases?
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protease inhibitor cocktail (Merck)
Can you add a product number for this cocktail, as well as a more complete description of what this cocktail is?
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