Temporin A and related frog antimicrobial peptides use formyl peptide receptor-like 1 as a receptor to chemoattract phagocytes.
Many mammalian antimicrobial peptides (AMPs) have multiple effects on antimicrobial immunity. We found that temporin A (TA), a representative frog-derived AMP, induced the migration of human monocytes, neutrophils, and macrophages with a bell-shaped response curve in a pertussis toxin-sensitive manner, activated p44/42 MAPK, and stimulated Ca(2+) flux in monocytes, suggesting that TA is capable of chemoattracting phagocytic leukocytes by the use of a G(ialpha) protein-coupled receptor. TA-induced Ca(2+) flux in monocytes was cross-desensitized by an agonistic ligand MMK-1 specific for formyl peptide receptor-like 1 (FPRL1) and vice versa, suggesting that TA uses FPRL1 as a receptor. This conclusion was confirmed by data showing that TA selectively stimulated chemotaxis of HEK 293 cells transfected with human FPRL1 or its mouse ortholog, murine formyl peptide receptor 2. In addition, TA elicited the infiltration of neutrophils and monocytes into the injection site of mice, indicating that TA is also functionally chemotactic in vivo. Examination of two additional temporins revealed that Rana-6 was also able to attract human phagocytes using FPRL1, but temporin 1P selectively induced the migration of neutrophils using a distinct receptor. Comparison of the chemotactic and antimicrobial activities of several synthetic analogues suggested that these activities are likely to rely on different structural characteristics. Overall, the results demonstrate that certain frog-derived temporins have the capacity to chemoattract phagocytes by the use of human FPRL1 (or its orthologs in other species), providing the first evidence suggesting the potential participation of certain amphibian antimicrobial peptides in host antimicrobial immunity.
Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702-1201, USA.
Qian
Q
Chen
David
D
Wade
Kahori
K
Kurosaka
Zhao Yuan
ZY
Wang
Joost J
JJ
Oppenheim
De
D
Yang
D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001001:Anura; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D020929:Mitogen-Activated Protein Kinase Kinases / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000276:immunology*; D010586:Phagocytes / Q000276:immunology*; D011506:Proteins / Q000276:immunology*; D044042:Receptors, Formyl Peptide; D043562:Receptors, G-Protein-Coupled / Q000276:immunology / Q000378:metabolism; D044067:Receptors, Lipoxin
D023181:Antimicrobial Cationic Peptides; D002630:Chemotactic Factors; C105101:FPR2 protein, human; D010455:Peptides; D011506:Proteins; D044042:Receptors, Formyl Peptide; D043562:Receptors, G-Protein-Coupled; D044067:Receptors, Lipoxin; C104501:temporin; D020929:Mitogen-Activated Protein Kinase Kinases