Variable responses of formyl peptide receptor haplotypes toward bacterial peptides.
The chemoattractant neutrophil formyl peptide receptor (FPR) binds bacterial and mitochondrial N-formylated peptides, which allows the neutrophils to find the bacterial source and/or site of tissue damage. Certain inflammatory disorders may be due in part to an impaired innate immune system that does not respond to acute bacterial damage in a timely fashion. Because the human FPR is encoded by a large number of different haplotypes arising from ten single-nucleotide polymorphisms, we examined the possibility that some of these haplotypes are functionally distinct. We analyzed the response of three common FPR haplotypes to peptides from Escherichia coli, Mycobacterium avium ssp. paratuberculosis, and human mitochondria. All three haplotypes responded similarly to the E. coli and mitochondrial peptides, whereas one required a higher concentration of the M. avium peptide fMFEDAVAWF for receptor downregulation, receptor signaling, and chemotaxis. This raises the possibility of additional bacterial species differences in functional responses among FPR variants and establishes a precedent with potentially important implications for our innate immune response against bacterial infections. We also investigated whether certain FPR haplotypes are associated with rheumatoid arthritis (RA) by sequencing FPR1 from 148 Caucasian individuals. The results suggested that FPR haplotypes do not significantly contribute toward RA.
Gripentrog
Jeannie M
JM
Department of Microbiology, Montana State University, MT 59717, USA.
Mills
John S
JS
Saari
George J
GJ
Miettinen
Heini M
HM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016466:CHO Cells; D002630:Chemotactic Factors; D006224:Cricetinae; D003412:Cricetulus; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008969:Molecular Sequence Data; D009162:Mycobacterium avium / Q000378:metabolism; D010283:Paratuberculosis / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D044042:Receptors, Formyl Peptide / Q000235:genetics* / Q000276:immunology; D014162:Transfection
D002630:Chemotactic Factors; D010446:Peptide Fragments; D044042:Receptors, Formyl Peptide; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3