Elsevier

Toxicology

Volume 87, Issues 1–3, 28 February 1994, Pages 131-149
Toxicology

Defensins: a family of antimicrobial and cytotoxic peptides

https://doi.org/10.1016/0300-483X(94)90158-9Get rights and content

Abstract

Defensins are antimicrobial and cytotoxic peptides that contain 29–35 amino acid residues, including 6 invariant cysteines that form 3 intramolecular disulfide bonds. They constitute more than 5% of the total cellular protein of human and rabbit neutrophils (PMN), and are also produced by rabbit lung macrophages and by murine and human small intestinal Paneth cells. Defensins exerted antimicrobial effects in vitro against many Gram-positive and Gram-negative bacteria, fungi, mycobacteria and some enveloped viruses, and were cytotoxic to a wide range of normal and malignant targets, including cells resistant to TNF-α and NK-cytolytic factor. Human and rabbit defensins formed voltage-sensitive channels in a variety of planar lipid bilayers when a negative voltage of ∼70–90 mV was applied to the contralateral side. These channels showed modest anion selectivity and their formation was strongly influenced by defensin concentration. Although most other channel-forming peptides have prominent α-helical domains, the structure of defensin molecules is primarily composed of antiparallel β-sheets. Studies with various prokaryotic and eukaryotic cells provided convincing evidence that defensins killed these targets by forming voltage-regulated channels in the susceptible cell's membrane. The broad spectrum of defensin-susceptible targets and the abundance of defensins in specialized host defense cells of the blood, lungs and intestinal tract suggest that defensins could play a significant role in innate immunity to infection and neoplasia.

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