Cathelicidin

2017-10-29T03:17:58Z

2001:250:500F:3EA:5940:9B11:704:F160: /* Characteristics */

{{Infobox_gene}}
'''Cathelicidin'''-related antimicrobial peptides are a family of [[polypeptides]] found in [[lysosomes]] of [[macrophage]]s and [[Granulocyte|polymorphonuclear leukocytes]] (PMNs), and [[Keratinocytes]].<ref>{{cite web | title = Entrez Gene: CAMP cathelicidin antimicrobial peptide| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=820| accessdate = }}</ref> Cathelicidins serve a critical role in mammalian innate immune defense against invasive bacterial infection.<ref name="Zanetti_2004"/> The cathelicidin family of peptides are classified as [[antimicrobial peptide]]s (AMPs). The AMP family also includes the [[defensin]]s. Whilst the defensins share common structural features, cathelicidin-related peptides are highly heterogeneous.<ref name="Zanetti_2004"/>

Members of the cathelicidin family of antimicrobial polypeptides are characterized by a highly conserved region (cathelin domain) and a highly variable cathelicidin peptide domain.<ref name="Zanetti_2004">{{cite journal | vauthors = Zanetti M | title = Cathelicidins, multifunctional peptides of the innate immunity | journal = Journal of Leukocyte Biology | volume = 75 | issue = 1 | pages = 39–48 | date = January 2004 | pmid = 12960280 | doi = 10.1189/jlb.0403147 }}</ref>

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 [[Epithelium|epithelial]] cells and [[macrophage]]s after activation by bacteria, viruses, fungi, or the hormone [[1,25-D]], which is the hormonally active form of [[vitamin D]].<ref name="pmid16497887">{{cite journal | vauthors = 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 | title = Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response | journal = Science | volume = 311 | issue = 5768 | pages = 1770–3 | date = March 2006 | pmid = 16497887 | doi = 10.1126/science.1123933 }}</ref>

==Characteristics==
{{Infobox protein family
| align = left
| Symbol = Cathelicidin
| Name = Cathelicidin
| image = PDB_1kwi_EBI.jpg
| width =
| caption = Crystal Structure Analysis of the Cathelicidin Motif of Protegrins
| Pfam = PF00666
| Pfam_clan = CL0121
| InterPro = IPR001894
| SMART =
| PROSITE = PDOC00729
| SCOP = 1lyp
| TCDB =
| OPM family = 236
| OPM protein = 2k6o
}}
Cathelicidins range in size from 12 to 80 amino acid residues and have a wide range of structures.<ref name="pmid10931440">{{cite journal | vauthors = Gennaro R, Zanetti M | title = Structural features and biological activities of the cathelicidin-derived antimicrobial peptides | journal = Biopolymers | volume = 55 | issue = 1 | pages = 31–49 | year = 2000 | pmid = 10931440 | doi = 10.1002/1097-0282(2000)55:1<31::AID-BIP40>3.0.CO;2-9 }}</ref> Most cathelicidins are linear peptides with 23-37 amino acid residues, and fold into amphipatic [[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.<ref name="Zanetti_2004"/>

The cathelicidin family shares primary sequence homology with the [[cystatin]]<ref name="pmid12713586">{{cite journal | vauthors = Zaiou M, Nizet V, Gallo RL | title = Antimicrobial and protease inhibitory functions of the human cathelicidin (hCAP18/LL-37) prosequence | journal = The Journal of Investigative Dermatology | volume = 120 | issue = 5 | pages = 810–6 | date = May 2003 | pmid = 12713586 | doi = 10.1046/j.1523-1747.2003.12132.x }}</ref> family of cysteine proteinase inhibitors, although amino acid residues thought to be important in such protease inhibition are usually lacking.
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== 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.<ref>{{cite journal | vauthors = Kościuczuk EM, Lisowski P, Jarczak J, Strzałkowska N, Jóźwik A, Horbańczuk J, Krzyżewski J, Zwierzchowski L, Bagnicka E | title = Cathelicidins: family of antimicrobial peptides. A review | language = en | journal = Molecular Biology Reports | volume = 39 | issue = 12 | pages = 10957–70 | date = December 2012 | pmid = 23065264 | pmc = 3487008 | doi = 10.1007/s11033-012-1997-x | url = https://link.springer.com/article/10.1007/s11033-012-1997-x }}</ref>

== 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:<ref name="Zanetti_2004"/>
{{div col|colwidth=20em}}
*Human: [[LL-37]] and [[hCAP-18]]
*Rhesus monkey: RL-37
*Mice:CRAMP-1/2, (Cathelicidin-related Antimicrobial Peptide<ref name="pmid9148921">{{cite journal | vauthors = Gallo RL, Kim KJ, Bernfield M, Kozak CA, Zanetti M, Merluzzi L, Gennaro R | title = Identification of CRAMP, a cathelin-related antimicrobial peptide expressed in the embryonic and adult mouse | journal = The Journal of Biological Chemistry | volume = 272 | issue = 20 | pages = 13088–93 | date = May 1997 | pmid = 9148921 | doi = 10.1074/jbc.272.20.13088 }}</ref>
*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]]'')<ref name="pmid22009138">{{cite journal | vauthors = Hao X, Yang H, Wei L, Yang S, Zhu W, Ma D, Yu H, Lai R | title = Amphibian cathelicidin fills the evolutionary gap of cathelicidin in vertebrate | journal = Amino Acids | volume = 43 | issue = 2 | pages = 677–85 | date = August 2012 | pmid = 22009138 | doi = 10.1007/s00726-011-1116-7 }}</ref>
*Sheep:
*Goats:
*Chickens: Four cathelicidins, fowlicidins 1,2,3 and cathelicidin Beta-1 <ref name="Achanta_2012">{{cite journal | vauthors = Achanta M, Sunkara LT, Dai G, Bommineni YR, Jiang W, Zhang G | title = Tissue expression and developmental regulation of chicken cathelicidin antimicrobial peptides | journal = Journal of Animal Science and Biotechnology | volume = 3 | issue = 1 | pages = 15 | date = May 2012 | pmid = 22958518 | pmc = 3436658 | doi = 10.1186/2049-1891-3-15 }}</ref>
*Horses:
*Pandas:
*Tasmanian Devil: Saha-CATH5 <ref>{{cite journal | vauthors = Peel E, Cheng Y, Djordjevic JT, Fox S, Sorrell TC, Belov K | title = Cathelicidins in the Tasmanian devil (Sarcophilus harrisii) | journal = Scientific Reports | volume = 6 | pages = 35019 | date = October 2016 | pmid = 27725697 | doi = 10.1038/srep35019 }}</ref>
*Salmonids: CATH1 and CATH2
{{Div col end}}

== Clinical significance ==

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 [[KLK7|kallikrein 7]] serine proteases. Excessive production of LL-37 is suspected to be a contributing cause in all subtypes of [[Rosacea]].<ref name="pmid22577261">{{cite journal | vauthors = Reinholz M, Ruzicka T, Schauber J | title = Cathelicidin LL-37: an antimicrobial peptide with a role in inflammatory skin disease | journal = Annals of Dermatology | volume = 24 | issue = 2 | pages = 126–35 | date = May 2012 | pmid = 22577261 | pmc = 3346901 | doi = 10.5021/ad.2012.24.2.126 }}</ref> Antibiotics have been used in the past to treat rosacea, but antibiotics may only work because they inhibit some SCTEs.<ref name="pmid17676051">{{cite journal | vauthors = 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 | title = Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea | journal = Nature Medicine | volume = 13 | issue = 8 | pages = 975–80 | date = August 2007 | pmid = 17676051 | doi = 10.1038/nm1616 }}</ref>

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.<ref name="pmid19133797">{{cite journal | vauthors = Gombart AF, Bhan I, Borregaard N, Tamez H, Camargo CA, Koeffler HP, Thadhani R | title = Low plasma level of cathelicidin antimicrobial peptide (hCAP18) predicts increased infectious disease mortality in patients undergoing hemodialysis | journal = Clinical Infectious Diseases | volume = 48 | issue = 4 | pages = 418–24 | date = February 2009 | pmid = 19133797 | doi = 10.1086/596314 | last5 = Camargo }}</ref>

Vitamin D up-regulates genetic expression of cathelicidin, which exhibits broad-spectrum microbicidal activity against bacteria, fungi, and viruses.<ref name="pmid11807545">{{cite journal | vauthors = Zasloff M | title = Antimicrobial peptides of multicellular organisms | journal = Nature | volume = 415 | issue = 6870 | pages = 389–95 | date = January 2002 | pmid = 11807545 | doi = 10.1038/415389a }}</ref><ref name="pmid20119827">{{cite journal | vauthors = Kamen DL, Tangpricha V | title = Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity | journal = Journal of Molecular Medicine | volume = 88 | issue = 5 | pages = 441–50 | date = May 2010 | pmid = 20119827 | pmc = 2861286 | doi = 10.1007/s00109-010-0590-9 }}</ref> Cathelicidin rapidly destroys the lipoprotein membranes of microbes enveloped in [[phagosome]]s after fusion with [[lysosome]]s in [[macrophage]]s.

== See also ==
* [[Antimicrobial peptides]]
* [[Innate immune system]]
* [[Richard Gallo]]
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== References ==
{{Reflist|33em}}

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

{{Granule contents}}
{{Pore-forming toxins}}

[[Category:Immune system]]
[[Category:Antimicrobial peptides]]
[[Category:Leukocytes]]
[[Category:Vitamin D]]
[[Category:Protein families]]

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Cathelicidin