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Am J Physiol Lung Cell Mol Physiol. 2019 Jan 31. doi: 10.1152/ajplung.00127.2018. [Epub ahead of print]

CD36 mediates albumin transcytosis by dermal but not lung microvascular endothelial cells - role in fatty acid delivery.

Author information

1
Institute of Medical Sciences, University of Toronto, Canada.
2
Laboratory Medicine and Pathobiology, University of Toronto, Canada.
3
St. Michael's Hospital.
4
University of Alberta.
5
Department of Microbiology and Immunology, University of Western Ontario.
6
Critical Care Medicine, St. Michael's Hospital, Canada.

Abstract

In healthy blood vessels, albumin crosses the endothelium to leave the circulation by transcytosis. However, little is known about the regulation of albumin transcytosis or how it differs in different tissues; its physiological purpose is also unclear. Using total internal reflection fluorescence microscopy, we quantified transcytosis of albumin across primary human microvascular endothelial cells from both lung and skin. We then validated our in vitro findings using a tissue-specific knockout mouse model. We observed that albumin transcytosis was saturable in the skin but not the lung microvascular endothelial cells, implicating a receptor-mediated process. We identified the scavenger receptor CD36 as being both necessary and sufficient for albumin transcytosis across dermal microvascular endothelium, in contrast to the lung where macropinocytosis dominated. Mutations in the apical helical bundle of CD36 prevented albumin internalization by cells. Mice deficient in CD36 specifically in endothelial cells exhibited lower basal permeability to albumin and less basal tissue edema in the skin but not in the lung. Finally, these mice also exhibited a smaller subcutaneous fat layer despite having identical total body weights and circulating fatty acid levels as wild-type animals. In conclusion, CD36 mediates albumin transcytosis in the skin but not the lung. Albumin transcytosis may serve to regulate fatty acid delivery from the circulation to tissues.

KEYWORDS:

CD36; albumin; endothelial; fatty acid; transcytosis

PMID:
30702342
DOI:
10.1152/ajplung.00127.2018

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