Variable responses of formyl peptide receptor haplotypes toward bacterial peptides |
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Authors: | Jeannie M Gripentrog John S Mills George J Saari Heini M Miettinen |
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Institution: | (1) Department of Microbiology, Montana State University, 109 Lewis Hall, Bozeman, MT 59717, USA;(2) Bozeman Deaconess Health Group and WWAMI Medical Education Program, Montana State University, Bozeman, MT 59717, USA |
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Abstract: | 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.
George J. Saari, Deceased. |
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Keywords: | Chemoattractant receptor Inflammation Chemotaxis Cell signaling Haplotype |
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