Cathelicidin

Cathelicidin-related antimicrobial peptides are a family of is_associated_with::polypeptides found in is_associated_with::lysosomes of is_associated_with::macrophages and polymorphonuclear leukocytes (PMNs). Cathelicidins serve a critical role in mammalian innate immune defense against invasive bacterial infection. The cathelicidin family of peptides are classified as antimicrobial peptides (AMPs). The AMP family also includes the defensins. Whilst the defensins share common structural features, cathelicidin-related peptides are highly heterogeneous.

Members of the cathelicidin family of antimicrobial polypeptides are characterized by a highly conserved region (cathelin domain) and a highly variable cathelicidin peptide domain.

Cathelicidin peptides have been isolated from many different species of is_associated_with::mammals. Cathelicidins were originally found in is_associated_with::neutrophils but have since been found in many other cells including epithelial cells and is_associated_with::macrophages after activation by bacteria, viruses, fungi, or the hormone is_associated_with::1,25-D, which is the hormonally active form of is_associated_with::vitamin D.

Characteristics
Cathelicidins range in size from 12 to 80 amino acid residues and have a wide range of structures. Most cathelicidins are linear peptides with 23-37 amino acid residues, and fold into amphiphatic is_associated_with::α-helices. Additionally cathelicidins may also be small-sized molecules (12-18 residues) with beta-hairpin structures, stabilized by one or two disulphide bonds. Even larger cathelicidin peptides (39-80 amino acid residues) are also present. These larger cathelicidins display repetitive is_associated_with::proline motifs forming extended polyproline-type structures.

The cathelicidin family shares primary sequence homology with the is_associated_with::cystatin family of cysteine proteinase inhibitors, although amino acid residues thought to be important in such protease inhibition are usually lacking.

Family members
Cathelicidin family components have been found in: humans, monkeys, mice, rats, rabbits, guinea pigs, pandas, pigs, cattle, frogs, sheep, goats, chickens, and horses.

Currently identified cathelicidins include the following:


 * Human:is_associated_with::hCAP-18/is_associated_with::LL-37
 * Rhesus Monkey: RL-37
 * Mice:is_associated_with::CRAMP-1/2, (Cathelicidin-related Antimicrobial Peptide
 * Rats: rCRAMP
 * Rabbits: CAP-18
 * Guinea Pig: CAP-11
 * Pigs: is_associated_with::PR-39, Prophenin, PMAP-23,36,37
 * Cattle: BMAP-27,28,34 (Bovine Myeloid Antimicrobial Peptides); Bac5, Bac7
 * Frogs: cathelicidin-AL (found in is_associated_with::Amolops loloensis)
 * Sheep:
 * Goats:
 * Chickens: Four cathelicidins, fowlicidins 1,2,3 and cathelicidin Beta-1
 * Horses:
 * Pandas:

Clinical significance
Patients with is_associated_with::rosacea have elevated levels of cathelicidin and elevated levels of stratum corneum tryptic enzymes (SCTEs). Cathelicidin is cleaved into the antimicrobial peptide LL-37 by both is_associated_with::kallikrein 5 and kallikrein 7 serine proteases. Excessive production of LL-37 is suspected to be a contributing cause in all subtypes of is_associated_with::Rosacea. Antibiotics have been used in the past to treat rosacea, but antibiotics may only work because they inhibit some SCTEs.

Higher levels of human cathelicidin antimicrobial protein (hCAP18), which are up-regulated by is_associated_with::vitamin D, appear to significantly reduce the risk of death from infection in is_associated_with::dialysis patients. Patients with a high level of this protein were 3.7 times more likely to survive kidney dialysis for a year without a fatal infection.

Vitamin D up-regulates genetic expression of cathelicidin, which exhibits broad-spectrum microbicidal activity against bacteria, fungi, and viruses. Cathelicidin rapidly destroys the lipoprotein membranes of microbes enveloped in is_associated_with::phagosomes after fusion with is_associated_with::lysosomes in is_associated_with::macrophages.