The study by Peluso and colleagues also brings the area of small antimicrobial proteins and peptides to the "radar screen" of rheumatologists because it is an area of increasing research and therapeutic interest in fields such as inflammatory bowel disease.
Therefore, it is important to review the major classes of the antimicrobial proteins and peptides.
Two classes of antimicrobial proteins and peptides that have received the most attention in recent years are the defensins and cathelicidins.
In settings such as the moist airways, gastrointestinal tract, and urinary tract, defensins are also secreted into the biofilm covering the epithelial surface, where they create a barrier that is chemically lethal to microbes. Certain of these antimicrobial peptides promote epithelial growth and angiogenesis.
Defensins are small (15-20 amino acid residue) cysteine-rich cationic proteins found in both vertebrates and invertebrates. They are active against bacteria, fungi, and enveloped viruses.
They consist of 30 to 45 amino acid precursors that are processed to final size 15-20 amino acids, including 6 to 8 conserved cysteine residues.
Defensins are very diverse with respect to amino acid sequence and secondary structure, but share certain properties, such as an affinity for the negatively charged phospholipids that are present on the outer surfaces of the cytoplasmic membranes of many microbial species.
Most defensins function by penetrating the microbial cell membrane by way of electrical attraction, and once embedded, forming a pore in the membrane that allows efflux.
The defensins are divided into 2 classes, alpha (a-) and beta (b-), on the basis of the differences in their secondary structures. More recently, a third class (theta defensins) was reported, but there is relatively little information about their role in normal health or disease.
a-Defensins were first discovered in the granules of white cells. Several years later, they were found in Paneth cells, the granule-containing cells that lie in the base of the crypts of the small intestine:
In white cells, a-defensins contribute to nonoxidative killing; and
In Paneth cells, they are secreted into the crypts and control the growth of bacteria in the small bowel.
b-Defensins: Four human b-defensins have been identified (although more than 20 genes appear to exist in our genome):
Human b-defensin 1 (HBD-1) is generally produced constitutively, whereas the others are inducible. In humans, b-defensins are synthesized by all epithelial tissues.
Another family of antimicrobial proteins is cathelicidins, which is a large and ancient class, traced from hagfish through humans. They are secreted in neutrophils and can be found in the bloodstream after infection. On epithelial surfaces, they function like defensins.
The salivary protein gene complex consists of a series of loci coding for related but distinct proline-rich proteins found chiefly in saliva, and to a lesser extent in respiratory tract secretions.
Human glandular salivary secretions contain several acidic proline-rich phosphoproteins. Amino acid sequences have shown that the two 150-residue molecules, proline-rich phosphoproteins-1 and proline-rich phosphoproteins-2 are closely related, while 2 related 106-residue proteins (proline-rich phosphoproteins-3 and proline-rich phosphoproteins-4) also show similarity. These proteins have important biologic functions related to providing a protective environment for the teeth, and appear to possess other activities associated with modulation of adhesion of bacteria to oral surfaces.
Studies of the physical properties of the proteins of human parotid saliva together with their inheritance patterns have led to the description of at least 10 discrete but genetically linked loci controlling the synthesis of a group of proline-rich proteins. These proteins also occur in the respiratory tract, suggesting that they could have some general functions unrelated to those conventionally ascribed to saliva.
The proline-rich proteins are characterized by a predominance of the amino acids proline (25% to 42%), glycine, and glutamic acid or glutamine. Together these 3 amino acids account for 70%-88% of the total amino acids in the proteins.
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Cite this: Proteomics, Saliva, and Sjögren's Syndrome - Medscape - Feb 20, 2008.