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By acting as a pro-defensin convertase in human Paneth cells, trypsin is involved in the regulation of innate immunity in the small intestine
Limited proteolysis is a highly specific irreversible process which serves to initiate physiological function by converting precursor proteins into biologically active forms. It can also be a mechanism for terminating biological activity. Limited proteolysis is used in a wide variety of biological systems, including blood coagulation, hormone regulation, and host defence.
Alpha defensins are small (∼29–35 amino acids) cationic disulphide linked peptides that are expressed mainly in neutrophils1,2 and Paneth cells (PCs) of the gastrointestinal tract.3–6 In mouse small intestine, multiple α-defensins (known as cryptdins) have been identified that constitute 70% of the released bactericidal activity.7 Human PCS express only two members (human defensins 5 (HD-5) and 6 (HD-6)) of this family of antimicrobial peptides.4,5 Functions attributed to PC derived defensins include regulation of the microbial density of the small intestine, protection of neighbouring stem cells in the crypt, and defence against pathogens.7–9 Defensins are synthesised as larger precursor molecules (∼100 amino acids) with a putative amino terminal signal sequence (which targets the peptide to the endoplasmic reticulum for eventual export), followed by …