Abstract

The era of genomics has arrived bringing with it the promise of novel insights into the molecular basis of human health and disease. True to this promise, the field of innate immunity has seen extraordinary advances in the identification of key molecules for pathogen recognition, cellular signalling and microbicidal activity. Prominent among them in both epithelial tissues and granulocytes are the abundant and evolutionary-ancient defensins and cathelicidins. These molecules, recognized initially for their broad-spectrum antimicrobial properties, are now shown to occupy critical junctions in both the regulatory and effector arms of the innate immune system. This review will focus on these unique peptides, highlighting their structure, function and regulation in epithelial host defence, with an emphasis on clinical implications and a role as therapeutic targets.

1. ANTIMICROBIAL PEPTIDES 1.1. Structures

The two salient features that identify an antimicrobial peptide are an ability to inactivate microorganisms, tested either in vitro or in vivo, and a size less than 100 amino acids. Given these rather broad definitions, over 500 molecules derived from either plant or animal species are now categorised as antimicrobial peptides [1-3]. As a general rule, they are derived from propeptides following constitutive or inducible processing. The active peptides vary in structure from disulfide-bridged circular peptides to amphipathic a-helical sequences enriched for a single amino acid (Fig. 1). A common feature is the formation of a tertiary structure permissive for interaction with the predominantly anionic, cholesterol-poor microbial membrane [4].

Many excellent reviews are available on the numerous classes of antimicrobial peptides, describing in a wealth of detail their gene, mRNA and peptide structures [5,6]. Here we will outline briefly the principle classes of antimicrobial peptides isolated from mammalian tissues, with particular emphasis on those from H. sapiens.

In the 1980's, investigators at UCLA published seminal work characterising neutrophil defensins, the most abundant class of mammalian antimicrobial peptides [5]. As a general rule, mammalian defensins are cationic, arginine-rich, cysteine-containing peptides 29-47 amino acids in length that are derived from larger, precursor molecules. Most commonly, these pre-

• Linear Helix LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES

Natural Treatments For Psoriasis

Natural Treatments For Psoriasis

Do You Suffer From the Itching and Scaling of Psoriasis? Or the Chronic Agony of Psoriatic Arthritis? If so you are not ALONE! A whopping three percent of the world’s populations suffer from either condition! An incredible 56 million working hours are lost every year by psoriasis sufferers according to the National Psoriasis Foundation.

Get My Free Ebook


Post a comment