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Citrullinated histone 3 causes endothelial barrier dysfunction.


ABSTRACT: Circulating components of neutrophil extracellular traps (NETs), especially histones, are associated with tissue injury during inflammatory conditions like sepsis. Commonly used as a NET biomarker, citrullinated histone 3 (H3Cit) may also functionally contribute to the NET-associated inflammatory response. To this end, we sought to examine the role of H3Cit in mediating microvascular endothelial barrier dysfunction. Here we show that H3Cit can directly contribute to inflammatory injury by disrupting the microvascular endothelial barrier. We found that endothelial responses to H3Cit are characterized by cell-cell adherens junction opening and cytoskeleton reorganization with increased F-actin stress fibers. Several signaling pathways often implicated in the transduction of hyperpermeability, such as Rho and MLCK, did not appear to play a major role; however, the adenylyl cyclase activator forskolin blocked the endothelial barrier effect of H3Cit. Taken together, the data suggest that H3Cit-induced endothelial barrier dysfunction may hold promise to treat inflammatory injury.

SUBMITTER: Meegan JE 

PROVIDER: S-EPMC6119499 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Citrullinated histone 3 causes endothelial barrier dysfunction.

Meegan Jamie E JE   Yang Xiaoyuan X   Beard Richard S RS   Jannaway Melanie M   Chatterjee Victor V   Taylor-Clark Thomas E TE   Yuan Sarah Y SY  

Biochemical and biophysical research communications 20180717 3


Circulating components of neutrophil extracellular traps (NETs), especially histones, are associated with tissue injury during inflammatory conditions like sepsis. Commonly used as a NET biomarker, citrullinated histone 3 (H3Cit) may also functionally contribute to the NET-associated inflammatory response. To this end, we sought to examine the role of H3Cit in mediating microvascular endothelial barrier dysfunction. Here we show that H3Cit can directly contribute to inflammatory injury by disrup  ...[more]

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