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In Focus: Formyl Peptide Receptors

Chemotactic factors from both Gram-positive and Gram-negative bacteria are short peptides with N-formyl methionine at the N-terminus (extensively reviewed in reference 1). These peptides are released from bacteria during infection and activate formyl peptide receptor (FPR), a member of G-protein coupled receptors (GPCRs). In humans, the FPR family consists mainly of three receptors, FPR1, FPR2/ALX (formerly FPRL1), and FPR3 (formerly FPRL2) which all couple to the Gi subtype of G-proteins and ultimately lead to the activation of phospholipase C and intracellular Ca2+ increase1,2.

FPRL1 or FPR2/ALX as commonly called is a seven transmembrane protein like all GPCRs. This receptor was originally cloned by screening a HL60 neutrophil cDNA library with a FPR1 cDNA probe3. FPR2/ALX shares 69% identity with FPR1 and despite its high homology, it displays relatively low affinity for fmlf, the most potent N-formyl peptide released by bacteria3.

FPR1 was originally found in neutrophils and later found to be distributed in myeloid and non-myeloid cells as is the case for FPR2/ALX and FPR3 (FPR3 though is not expressed in neutrophils). FPR1 is also expressed in multiple organs and tissues including epithelial cells in organs with secretory functions, endocrine cells, liver hepathocytes, smooth muscle cells and endothelial cells, brain spinal cord and both motor and sensory neurons4. FPR2/ALX has a similar tissue distribution to that of FPR1.

While N-formyl peptides were the first peptides found to activate these receptors, the ligand diversity for FPR has proven to be quite broad and demonstrates to be both pro- and anti-inflammatory. They include peptidic ligands originating from bacterial and viral sources (including HIV), endogenous ligands such as chemokines and annexins, short peptides associated with inflammation and infection. Indeed, peptides from Herpes, Ebola and coronavirus 229E are ligands of FPR11.

Alomone Labs is pleased to offer Anti-Human FPR1 (extracellular) antibody (#AFR-001), Anti-Human FPR1 (extracellular)-ATTO Fluor-488 antibody (#AFR-001-AG) and Anti-Human FPR2/ALX (extracellular) antibody (#AFR-002). All three antibodies are directed against extracellular epitopes and have been validated in indirect/direct flow cytometry. We are also pleased to offer a number of peptide agonists and agonists acting on these receptors.

References

  1. Ye, R.D. et al. (2009) Pharmacol. Rev. 61, 119.
  2. Le, Y. et al. (2002) Trends Immunol. 23, 541.
  3. Murphy, P.M. et al. (1992) J. Biol. Chem. 267, 7637.
  4. Becker, E.L. (1998) Cell Tissue Res. 292, 129.