α Defensin Control of Inflammation Save

Alpha defensins are released following apoptosis, necrosis, or netosis of human neutrophils. They are taken up by other cells and microbes, wherein they permeablize membranes and kill microbes and host cells. Thus, they augment the antimicrobial capacity of macrophages and at the same time inhibit the biosynthesis of proinflammatory cytokines. They have been shown to have a protective effect when administered in animal models of inflammation. 

Brook and coworkers have published in PNAS that the antiinflammatory effects are mediated by the most abundant neutrophil alpha defensin, Human Neutrophil Peptide 1 (HNP1). HNP1 accumulates in macrophages and inhibits protein translation by binding nonspecifically to RNA but does not alter mRNA transcription or stability.

This finding is novel in that it is the first demonstration of a peptide released from one cell type (neutrophils) directly regulating mRNA translation in another (macrophages).

By preventing protein translation, HNP1 functions as a "molecular brake" on macrophage-driven inflammation, ensuring both pathogen clearance and the limitation of inflammation with minimal bystander or collateral tissue damage.

Such a finding may have major therapeutic implications in chronic inflammatory conditions wherein the development of defensin-like peptides could yield both antiinflammatory and antimicrobial effects.