Mouse cathelin-related antimicrobial peptide chemoattracts leukocytes using formyl peptide receptor-like 1/mouse formyl peptide receptor-like 2 as the receptor and acts as an immune adjuvant
- PMID: 15879124
- DOI: 10.4049/jimmunol.174.10.6257
Mouse cathelin-related antimicrobial peptide chemoattracts leukocytes using formyl peptide receptor-like 1/mouse formyl peptide receptor-like 2 as the receptor and acts as an immune adjuvant
Abstract
Mammalian antimicrobial proteins, such as defensins and cathelicidin, have stimulating effects on host leukocytes. Cathelin-related antimicrobial peptide (CRAMP), the orthologue of human cathelicidin/LL-37, is the sole identified murine cathelicidin. CRAMP has been shown to have both antimicrobial and angiogenic activities. However, whether CRAMP, like human cathelicidin/LL-37, also exhibits a direct effect on the migration and function of leukocytes is not known. We have observed that CRAMP, like LL-37, was chemotactic for human monocytes, neutrophils, macrophages, and mouse peripheral blood leukocytes. CRAMP also induced calcium mobilization and the activation of MAPK in monocytes. CRAMP-induced calcium flux in monocytes was desensitized by MMK-1, an agonistic ligand specific for formyl peptide receptor-like-1 (FPRL1), and vice versa, suggesting the use of FPRL1 by CRAMP as a receptor. Furthermore, CRAMP induced the chemotaxis of human embryonic kidney 293 cells transfected with either FPRL1 or mouse formyl peptide receptor-2, the mouse homologue of FPRL1, but not by untransfected parental human embryonic kidney 293 cells, confirming the use of FPRL1/mouse formyl peptide receptor-2 by CRAMP. Injection of CRAMP into mouse air pouches resulted in the recruitment predominantly of neutrophils and monocytes, indicating that CRAMP acts as a chemotactic factor in vivo. Finally, simultaneous administration of OVA with CRAMP to mice promoted both humoral and cellular Ag-specific immune responses. Thus, CRAMP functions as both a chemoattractant for phagocytic leukocytes and an enhancer of adaptive immune response.
Similar articles
-
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.J Exp Med. 2000 Oct 2;192(7):1069-74. doi: 10.1084/jem.192.7.1069. J Exp Med. 2000. PMID: 11015447 Free PMC article.
-
Temporin A and related frog antimicrobial peptides use formyl peptide receptor-like 1 as a receptor to chemoattract phagocytes.J Immunol. 2004 Aug 15;173(4):2652-9. doi: 10.4049/jimmunol.173.4.2652. J Immunol. 2004. PMID: 15294982
-
An antimicrobial cathelicidin peptide, human CAP18/LL-37, suppresses neutrophil apoptosis via the activation of formyl-peptide receptor-like 1 and P2X7.J Immunol. 2006 Mar 1;176(5):3044-52. doi: 10.4049/jimmunol.176.5.3044. J Immunol. 2006. PMID: 16493063
-
Participation of mammalian defensins and cathelicidins in anti-microbial immunity: receptors and activities of human defensins and cathelicidin (LL-37).J Leukoc Biol. 2001 May;69(5):691-7. J Leukoc Biol. 2001. PMID: 11358975 Review.
-
A new insight into the role of "old" chemotactic peptide receptors FPR and FPRL1: down-regulation of chemokine receptors CCR5 and CXCR4.Forum (Genova). 1999 Oct-Dec;9(4):299-314. Forum (Genova). 1999. PMID: 10611407 Review.
Cited by
-
Antimicrobial peptide LL-37 ameliorates a murine sepsis model via the induction of microvesicle release from neutrophils.Innate Immun. 2020 Oct;26(7):565-579. doi: 10.1177/1753425920936754. Epub 2020 Jun 29. Innate Immun. 2020. PMID: 32600088 Free PMC article.
-
Signal relay by CC chemokine receptor 2 (CCR2) and formylpeptide receptor 2 (Fpr2) in the recruitment of monocyte-derived dendritic cells in allergic airway inflammation.J Biol Chem. 2013 Jun 7;288(23):16262-16273. doi: 10.1074/jbc.M113.450635. Epub 2013 Apr 19. J Biol Chem. 2013. PMID: 23603910 Free PMC article.
-
A member of the cathelicidin family of antimicrobial peptides is produced in the upper airway of the chinchilla and its mRNA expression is altered by common viral and bacterial co-pathogens of otitis media.Mol Immunol. 2007 Mar;44(9):2446-58. doi: 10.1016/j.molimm.2006.10.008. Epub 2006 Nov 20. Mol Immunol. 2007. PMID: 17113647 Free PMC article.
-
Murine and Human Cathelicidins Contribute Differently to Hallmarks of Mastitis Induced by Pathogenic Prototheca bovis Algae.Front Cell Infect Microbiol. 2020 Feb 7;10:31. doi: 10.3389/fcimb.2020.00031. eCollection 2020. Front Cell Infect Microbiol. 2020. PMID: 32117805 Free PMC article.
-
The formylpeptide receptor 2 (Fpr2) and its endogenous ligand cathelin-related antimicrobial peptide (CRAMP) promote dendritic cell maturation.J Biol Chem. 2014 Jun 20;289(25):17553-63. doi: 10.1074/jbc.M113.535674. Epub 2014 May 7. J Biol Chem. 2014. PMID: 24808174 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases