title: Regulation of the formyl peptide receptor 1 (FPR1) gene in primary human macrophages.
abstract: The formyl peptide receptor 1 (FPR1) is mainly expressed by mammalian phagocytic leukocytes and plays a role in chemotaxis, killing of microorganisms through phagocytosis, and the generation of reactive oxygen species. A large number of ligands have been identified triggering FPR1 including formylated and non-formylated peptides of microbial and endogenous origin. While the expression of FPR1 in neutrophils has been investigated intensively, knowledge on the regulation of FPR1 expression in polarized macrophages is lacking. In this study we show that primary human neutrophils, monocytes and resting macrophages do express the receptor on their cell surface. Polarization of macrophages with IFNγ, LPS and with the TLR8 ligand 3M-002 further increases FPR1 mRNA levels but does not consistently increase protein expression or chemotaxis towards the FPR1 ligand fMLF. In contrast, polarization of primary human macrophages with IL-4 and IL-13 leading to the alternative activated macrophages, reduces FPR1 cell surface expression and abolishes chemotaxis towards fMLF. These results show that M2 macrophages will not react to triggering of FPR1, limiting the role for FPR1 to chemotaxis and superoxide production of resting and pro-inflammatory M1 macrophages.
authors.affiliation: Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, Switzerland.
authors.forename: Claudio
authors.initials: C
authors.lastname: Gemperle
authors.forename: Mattia
authors.initials: M
authors.lastname: Schmid
authors.forename: Magdalena
authors.initials: M
authors.lastname: Herova
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Marti-Jaun
authors.forename: Sophia J A
authors.initials: SJ
authors.lastname: Wuest
authors.forename: Christa
authors.initials: C
authors.lastname: Loretz
authors.forename: Martin
authors.initials: M
authors.lastname: Hersberger
mesh_terms: D002633:Chemotaxis / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D061251:Primary Cell Culture; D011804:Quinolines / Q000494:pharmacology; D044042:Receptors, Formyl Peptide / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: C526117:3M 002; C469986:FPR1 protein, human; D007093:Imidazoles; D018793:Interleukin-13; D008070:Lipopolysaccharides; D011804:Quinolines; D044042:Receptors, Formyl Peptide; D013481:Superoxides; D015847:Interleukin-4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D007371:Interferon-gamma