regulation of the formyl peptide receptor 1 (fpr1) gene in primary human macrophages监管甲酰肽受体1(fpr1)基因在人类巨噬细胞主要.pdfVIP

Regulation of the Formyl Peptide Receptor 1 (FPR1) Gene in Primary Human Macrophages Claudio Gemperle1,2,3., Mattia Schmid1,2,3., Magdalena Herova1,2,3, Jacqueline Marti-Jaun1,2,3, Sophia J. A. Wuest1,2,3, Christa Loretz1,2,3, Martin Hersberger1,2,3* 1 Division of Clinical Chemistry and Biochemistry, University Children’s Hospital Zurich, Zurich, Switzerland, 2 Children’s Research Center, University Children’s Hospital Zurich, Zurich, Switzerland, 3 Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland 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 IFNc, 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. Citation: Gemperle