Identification of novel peptides that stimulate human neutrophils

Neutrophils play a key role in innate immunity, and the identification of new stimuli that stimulate neutrophil activity is a very important issue. In this study, we identified three novel peptides by screening a synthetic hexapeptide combinatorial library. The identified peptides GMMWAI, MMHWAM, and MMHWFM caused an increase in intracellular Ca2+ in a concentration-dependent manner via phospholipase C activity in human neutrophils. The three peptides acted specifically on neutrophils and monocytes and not on other non-leukocytic cells. As a physiological characteristic of the peptides, we observed that the three peptides induced chemotactic migration of neutrophils as well as stimulated superoxide anion production. Studying receptor specificity, we observed that two of the peptides (GMMWAI and MMHWFM) acted on formyl peptide receptor (FPR)1 while the other peptide (MMHWAM) acted on FPR2. Since the three novel peptides were specific agonists for FPR1 or FPR2, they might be useful tools to study FPR1- or FPR2-mediated immune response and signaling.

Association of SNPs in N-formylpeptide receptor gene with susceptibility of aggressive periodontitis / 北京大学学报(医学版)

Objective: To explore the association of the single nucleotide polymorphisms (SNPs) in N-formylpeptide receptor (FPR) gene with the susceptibility of aggressive periodontitis (AgP). Methods: A total of 94 AgP patients and 73 healthy controls were entered into the study. Peripheral blood sample was obtained from each subject by venepuncture. Genomic DNA was isolated from each sample.The target fragment of FPR gene was amplified by PCR. The SNPs in FPR gene were detected by denature high performance liquid chromatography ( DHPLC) combined with DNA sequencing. Results: There were two non-synonymous SNPs in the 370 bp FPR gene fragment;289C/A and 301G/C. The 289C/Awas a novel SNP. No variation in nucleotides 329 and 378 was detected. There were no statistically significant differences in distributions of the genotypes and alleles for FPR289 and FPR301 between AgP patients and healthy controls. Using multivariate logistic regression (adjusted for age and gender) , it was showed that the adjusted Ors of AgP for the C~+ genotype and allele C of FPR301 combined with smoking were 5.74 and 5.20 respectively. Conclusion: The presence of the C~+ genotype/allele C of FPR301 together with smoking conferred a higher risk for AgP. The result suggests that the SNPs in FPR gene may not be associated with the susceptibility of AgP in Chinese.

Lysophosphatidylglycerol inhibits formyl peptide receptor like-1-stimulated chemotactic migration and IL-1beta production from human phagocytes

In this study, we observed that lysophosphatidylglycerol (LPG) completely inhibited a formyl peptide receptor like-1 (FPRL1) agonist (MMK-1)-stimulated chemotactic migration in human phagocytes, such as neutrophils and monocytes. LPG also dramatically inhibited IL-1beta production by another FPRL1 agonist serum amyloid A (SAA) in human phagocytes. However, LPG itself induced intracellular calcium increase and superoxide anion production in human phagocytes. Keeping in mind that phagocytes migration and IL-1beta production by FPRL1 are important for the induction of inflammatory response, our data suggest that LPG can be regarded as a useful material for the modulation of inflammatory response induced by FPRL1 activation.