Cathelicidin

CAMP
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCAMP, CAP-18, CAP18, CRAMP, FALL-39, FALL39, HSD26, LL37, cathelicidin antimicrobial peptide
External IDsOMIM: 600474 MGI: 108443 HomoloGene: 110678 GeneCards: CAMP
Gene location (Human)
Chr.Chromosome 3 (human)[1]
Band3p21.31Start48,223,347 bp[1]
End48,225,491 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

820

12796

Ensembl

ENSG00000164047

ENSMUSG00000038357

UniProt

P49913

P51437

RefSeq (mRNA)

NM_004345

NM_009921

RefSeq (protein)

NP_004336

NP_034051

Location (UCSC)Chr 3: 48.22 – 48.23 MbChr 9: 109.85 – 109.85 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Cathelicidin-related antimicrobial peptides are a family of polypeptides primarily stored in the lysosomes of macrophages and polymorphonuclear leukocytes (PMNs).[5] Cathelicidins serve a critical role in mammalian innate immune defense against invasive bacterial infection.[6] 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.[6]

Members of the cathelicidin family of antimicrobial polypeptides are characterized by a highly conserved region (cathelin domain) and a highly variable cathelicidin peptide domain.[6]

Cathelicidin peptides have been isolated from many different species of mammals. Cathelicidins were originally found in neutrophils, but have since been found in many other cells including epithelial cells and macrophages after activation by bacteria, viruses, fungi, or the hormone 1,25-D, which is the hormonally active form of vitamin D.[7] The protein encoded by the human cathelicidin gene, CAMP, is cleaved into the LL-37 peptide, which has several immunological functions.

Characteristics

Cathelicidin
Crystal Structure Analysis of the Cathelicidin Motif of Protegrins
Identifiers
Symbol Cathelicidin
Pfam PF00666
Pfam clan CL0121
InterPro IPR001894
PROSITE PDOC00729
SCOP 1lyp
SUPERFAMILY 1lyp
OPM superfamily 209
OPM protein 2k6o

Cathelicidins range in size from 12 to 80 amino acid residues and have a wide range of structures.[8] Most cathelicidins are linear peptides with 23-37 amino acid residues, and fold into amphipathic 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 proline motifs forming extended polyproline-type structures.[6]

The cathelicidin family shares primary sequence homology with the cystatin[9] family of cysteine proteinase inhibitors, although amino acid residues thought to be important in such protease inhibition are usually lacking.

Mechanism of antimicrobial activity

The general rule of the mechanism triggering cathelicidin action, like that of other antimicrobial peptides, involves the disintegration (damaging and puncturing) of cell membranes of organisms toward which the peptide is active.[10]

Mammalian orthologs

Cathelicidin peptides 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:[6]

  • Human: hCAP-18 (cleaved into LL-37 and FALL-39)
  • Rhesus monkey: RL-37
  • Mice:CRAMP-1/2, (Cathelicidin-related Antimicrobial Peptide[11]
  • Rats: rCRAMP
  • Rabbits: CAP-18
  • Guinea pig: CAP-11
  • Pigs: PR-39, Prophenin, PMAP-23,36,37
  • Cattle: BMAP-27,28,34 (Bovine Myeloid Antimicrobial Peptides); Bac5, Bac7
  • Frogs: cathelicidin-AL (found in Amolops loloensis)[12]
  • Sheep:
  • Goats:
  • Chickens: Four cathelicidins, fowlicidins 1,2,3 and cathelicidin Beta-1 [13]
  • Horses:
  • Pandas:
  • Tasmanian Devil: Saha-CATH5 [14]
  • Salmonids: CATH1 and CATH2

Clinical significance

NOTE: This article seems to be split between two pages. More about cathelicidin's clinical significance can be found on the page for its encoding gene, LL-37.

Patients 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 kallikrein 5 and kallikrein 7 serine proteases. Excessive production of LL-37 is suspected to be a contributing cause in all subtypes of Rosacea.[15] Antibiotics have been used in the past to treat rosacea, but antibiotics may only work because they inhibit some SCTEs.[16]

Higher plasma levels of human cathelicidin antimicrobial protein (hCAP18), which are up-regulated by vitamin D, appear to significantly reduce the risk of death from infection in 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.[17]

Vitamin D up-regulates genetic expression of cathelicidin, which exhibits broad-spectrum microbicidal activity against bacteria, fungi, and viruses.[18][19] Cathelicidin rapidly destroys the lipoprotein membranes of microbes enveloped in phagosomes after fusion with lysosomes in macrophages.

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000164047 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000038357 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:".
  4. ↑ "Mouse PubMed Reference:".
  5. ↑ "Entrez Gene: CAMP cathelicidin antimicrobial peptide".
  6. 1 2 3 4 5 Zanetti M (January 2004). "Cathelicidins, multifunctional peptides of the innate immunity". Journal of Leukocyte Biology. 75 (1): 39–48. doi:10.1189/jlb.0403147. PMID 12960280.
  7. ↑ Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C, Kamen DL, Wagner M, Bals R, Steinmeyer A, Zügel U, Gallo RL, Eisenberg D, Hewison M, Hollis BW, Adams JS, Bloom BR, Modlin RL (March 2006). "Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response". Science. 311 (5768): 1770–3. doi:10.1126/science.1123933. PMID 16497887.
  8. ↑ Gennaro R, Zanetti M (2000). "Structural features and biological activities of the cathelicidin-derived antimicrobial peptides". Biopolymers. 55 (1): 31–49. doi:10.1002/1097-0282(2000)55:1<31::AID-BIP40>3.0.CO;2-9. PMID 10931440.
  9. ↑ Zaiou M, Nizet V, Gallo RL (May 2003). "Antimicrobial and protease inhibitory functions of the human cathelicidin (hCAP18/LL-37) prosequence". The Journal of Investigative Dermatology. 120 (5): 810–6. doi:10.1046/j.1523-1747.2003.12132.x. PMID 12713586.
  10. ↑ Kościuczuk EM, Lisowski P, Jarczak J, Strzałkowska N, Jóźwik A, Horbańczuk J, Krzyżewski J, Zwierzchowski L, Bagnicka E (December 2012). "Cathelicidins: family of antimicrobial peptides. A review". Molecular Biology Reports. 39 (12): 10957–70. doi:10.1007/s11033-012-1997-x. PMC 3487008. PMID 23065264.
  11. ↑ Gallo RL, Kim KJ, Bernfield M, Kozak CA, Zanetti M, Merluzzi L, Gennaro R (May 1997). "Identification of CRAMP, a cathelin-related antimicrobial peptide expressed in the embryonic and adult mouse". The Journal of Biological Chemistry. 272 (20): 13088–93. doi:10.1074/jbc.272.20.13088. PMID 9148921.
  12. ↑ Hao X, Yang H, Wei L, Yang S, Zhu W, Ma D, Yu H, Lai R (August 2012). "Amphibian cathelicidin fills the evolutionary gap of cathelicidin in vertebrate". Amino Acids. 43 (2): 677–85. doi:10.1007/s00726-011-1116-7. PMID 22009138.
  13. ↑ Achanta M, Sunkara LT, Dai G, Bommineni YR, Jiang W, Zhang G (May 2012). "Tissue expression and developmental regulation of chicken cathelicidin antimicrobial peptides". Journal of Animal Science and Biotechnology. 3 (1): 15. doi:10.1186/2049-1891-3-15. PMC 3436658. PMID 22958518.
  14. ↑ Peel E, Cheng Y, Djordjevic JT, Fox S, Sorrell TC, Belov K (October 2016). "Cathelicidins in the Tasmanian devil (Sarcophilus harrisii)". Scientific Reports. 6: 35019. doi:10.1038/srep35019. PMC 5057115. PMID 27725697.
  15. ↑ Reinholz M, Ruzicka T, Schauber J (May 2012). "Cathelicidin LL-37: an antimicrobial peptide with a role in inflammatory skin disease". Annals of Dermatology. 24 (2): 126–35. doi:10.5021/ad.2012.24.2.126. PMC 3346901. PMID 22577261.
  16. ↑ Yamasaki K, Di Nardo A, Bardan A, Murakami M, Ohtake T, Coda A, Dorschner RA, Bonnart C, Descargues P, Hovnanian A, Morhenn VB, Gallo RL (August 2007). "Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea". Nature Medicine. 13 (8): 975–80. doi:10.1038/nm1616. PMID 17676051.
  17. ↑ Gombart AF, Bhan I, Borregaard N, Tamez H, Camargo CA, Koeffler HP, Thadhani R (February 2009). "Low plasma level of cathelicidin antimicrobial peptide (hCAP18) predicts increased infectious disease mortality in patients undergoing hemodialysis". Clinical Infectious Diseases. 48 (4): 418–24. doi:10.1086/596314. PMID 19133797.
  18. ↑ Zasloff M (January 2002). "Antimicrobial peptides of multicellular organisms". Nature. 415 (6870): 389–95. doi:10.1038/415389a. PMID 11807545.
  19. ↑ Kamen DL, Tangpricha V (May 2010). "Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity". Journal of Molecular Medicine. 88 (5): 441–50. doi:10.1007/s00109-010-0590-9. PMC 2861286. PMID 20119827.

Further reading

  • Dürr UH, Sudheendra US, Ramamoorthy A (September 2006). "LL-37, the only human member of the cathelicidin family of antimicrobial peptides". Biochimica et Biophysica Acta. 1758 (9): 1408–25. doi:10.1016/j.bbamem.2006.03.030. PMID 16716248.
  • Chromek M, Slamová Z, Bergman P, Kovács L, Podracká L, Ehrén I, Hökfelt T, Gudmundsson GH, Gallo RL, Agerberth B, Brauner A (June 2006). "The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection". Nature Medicine. 12 (6): 636–41. doi:10.1038/nm1407. PMID 16751768.
  • Gombart AF, Borregaard N, Koeffler HP (July 2005). "Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3". FASEB Journal. 19 (9): 1067–77. doi:10.1096/fj.04-3284com. PMID 15985530.
  • López-García B, Lee PH, Gallo RL (May 2006). "Expression and potential function of cathelicidin antimicrobial peptides in dermatophytosis and tinea versicolor". The Journal of Antimicrobial Chemotherapy. 57 (5): 877–82. doi:10.1093/jac/dkl078. PMID 16556635.
  • Lehrer RI, Ganz T (January 2002). "Cathelicidins: a family of endogenous antimicrobial peptides". Current Opinion in Hematology. 9 (1): 18–22. doi:10.1097/00062752-200201000-00004. PMID 11753073.
  • Niyonsaba F, Hirata M, Ogawa H, Nagaoka I (September 2003). "Epithelial cell-derived antibacterial peptides human beta-defensins and cathelicidin: multifunctional activities on mast cells". Current Drug Targets. Inflammation and Allergy. 2 (3): 224–31. doi:10.2174/1568010033484115. PMID 14561157.
  • van Wetering S, Tjabringa GS, Hiemstra PS (April 2005). "Interactions between neutrophil-derived antimicrobial peptides and airway epithelial cells". Journal of Leukocyte Biology. 77 (4): 444–50. doi:10.1189/jlb.0604367. PMID 15591123.
  • Agerberth B, Gunne H, Odeberg J, Kogner P, Boman HG, Gudmundsson GH (January 1995). "FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis". Proceedings of the National Academy of Sciences of the United States of America. 92 (1): 195–9. doi:10.1073/pnas.92.1.195. PMC 42844. PMID 7529412.
  • Cowland JB, Johnsen AH, Borregaard N (July 1995). "hCAP-18, a cathelin/pro-bactenecin-like protein of human neutrophil specific granules". FEBS Letters. 368 (1): 173–6. doi:10.1016/0014-5793(95)00634-L. PMID 7615076.
  • Gudmundsson GH, Magnusson KP, Chowdhary BP, Johansson M, Andersson L, Boman HG (July 1995). "Structure of the gene for porcine peptide antibiotic PR-39, a cathelin gene family member: comparative mapping of the locus for the human peptide antibiotic FALL-39". Proceedings of the National Academy of Sciences of the United States of America. 92 (15): 7085–9. doi:10.1073/pnas.92.15.7085. PMC 41476. PMID 7624374.
  • Larrick JW, Hirata M, Balint RF, Lee J, Zhong J, Wright SC (April 1995). "Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein". Infection and Immunity. 63 (4): 1291–7. PMC 173149. PMID 7890387.
  • Gudmundsson GH, Agerberth B, Odeberg J, Bergman T, Olsson B, Salcedo R (June 1996). "The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes". European Journal of Biochemistry. 238 (2): 325–32. doi:10.1111/j.1432-1033.1996.0325z.x. PMID 8681941.
  • Larrick JW, Lee J, Ma S, Li X, Francke U, Wright SC, Balint RF (November 1996). "Structural, functional analysis and localization of the human CAP18 gene". FEBS Letters. 398 (1): 74–80. doi:10.1016/S0014-5793(96)01199-4. PMID 8946956.
  • Frohm M, Agerberth B, Ahangari G, Stâhle-Bäckdahl M, Lidén S, Wigzell H, Gudmundsson GH (June 1997). "The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders". The Journal of Biological Chemistry. 272 (24): 15258–63. doi:10.1074/jbc.272.24.15258. PMID 9182550.
  • Bals R, Wang X, Zasloff M, Wilson JM (August 1998). "The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface". Proceedings of the National Academy of Sciences of the United States of America. 95 (16): 9541–6. doi:10.1073/pnas.95.16.9541. PMC 21374. PMID 9689116.
  • Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, Oppenheim JJ, Chertov O (October 2000). "LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells". The Journal of Experimental Medicine. 192 (7): 1069–74. doi:10.1084/jem.192.7.1069. PMC 2193321. PMID 11015447.
  • Agerberth B, Charo J, Werr J, Olsson B, Idali F, Lindbom L, Kiessling R, Jörnvall H, Wigzell H, Gudmundsson GH (November 2000). "The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations". Blood. 96 (9): 3086–93. PMID 11049988.
  • Bals R, Lang C, Weiner DJ, Vogelmeier C, Welsch U, Wilson JM (March 2001). "Rhesus monkey (Macaca mulatta) mucosal antimicrobial peptides are close homologues of human molecules". Clinical and Diagnostic Laboratory Immunology. 8 (2): 370–5. doi:10.1128/CDLI.8.2.370-375.2001. PMC 96065. PMID 11238224.
  • Nagaoka I, Hirota S, Niyonsaba F, Hirata M, Adachi Y, Tamura H, Heumann D (September 2001). "Cathelicidin family of antibacterial peptides CAP18 and CAP11 inhibit the expression of TNF-alpha by blocking the binding of LPS to CD14(+) cells". Journal of Immunology. 167 (6): 3329–38. doi:10.4049/jimmunol.167.6.3329. PMID 11544322.
  • Hase K, Eckmann L, Leopard JD, Varki N, Kagnoff MF (February 2002). "Cell differentiation is a key determinant of cathelicidin LL-37/human cationic antimicrobial protein 18 expression by human colon epithelium". Infection and Immunity. 70 (2): 953–63. doi:10.1128/IAI.70.2.953-963.2002. PMC 127717. PMID 11796631.
  • Giuliani A, Pirri G, Nicoletto S (2007). "Antimicrobial peptides: an overview of a promising class of therapeutics". Cent. Eur. J. Biol. 2 (1): 1–33. doi:10.2478/s11535-007-0010-5.
  • Burton MF, Steel PG (December 2009). "The chemistry and biology of LL-37". Natural Product Reports. 26 (12): 1572–84. doi:10.1039/b912533g. PMID 19936387.
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