Journal article

Oxidative cross-linking of calprotectin occurs in vivo, altering its structure and susceptibility to proteolysis

Teagan S Hoskin, Jennifer M Crowther, Jeanette Cheung, Michael J Epton, Peter D Sly, Peter A Elder, Renwick CJ Dobson, Anthony J Kettle, Nina Dickerhof

Redox Biology | ELSEVIER | Published : 2019

Abstract

Calprotectin, the major neutrophil protein, is a critical alarmin that modulates inflammation and plays a role in host immunity by strongly binding trace metals essential for bacterial growth. It has two cysteine residues favourably positioned to act as a redox switch. Whether their oxidation occurs in vivo and affects the function of calprotectin has received little attention. Here we show that in saliva from healthy adults, and in lavage fluid from the lungs of patients with respiratory diseases, a substantial proportion of calprotectin was cross-linked via disulfide bonds between the cysteine residues on its S100A8 and S100A9 subunits. Stimulated human neutrophils released calprotectin an..

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Grants

Awarded by Health Research Council of New Zealand


Awarded by National Health and Medical Research Council, Australia


Awarded by Cystic Fibrosis Foundation, USA


Awarded by Cystic Fibrosis Australia


Funding Acknowledgements

This research was supported by the Health Research Council of New Zealand (15/333). AREST CF is supported by grants from the National Health and Medical Research Council, Australia (403911, 458513, 1002035, 1102590), the Cystic Fibrosis Foundation, USA (CFFT SLY4AO and STICK09AO), and Cystic Fibrosis Australia (1021316).