title: The Neutrophil Response Induced by an Agonist for Free Fatty Acid Receptor 2 (GPR43) Is Primed by Tumor Necrosis Factor Alpha and by Receptor Uncoupling from the Cytoskeleton but Attenuated by Tissue Recruitment.
abstract: Ligands with improved potency and selectivity for free fatty acid receptor 2 (FFA2R) have become available, and we here characterize the neutrophil responses induced by one such agonist (Cmp1) and one antagonist (CATPB). Cmp1 triggered an increase in the cytosolic concentration of Ca(2+), and the neutrophils were then desensitized to Cmp1 and to acetate, a naturally occurring FFA2R agonist. The antagonist CATPB selectively inhibited responses induced by Cmp1 or acetate. The activated FFA2R induced superoxide anion secretion at a low level in naive blood neutrophils. This response was largely increased by tumor necrosis factor alpha (TNF-α) in a process associated with a recruitment of easily mobilizable granules, but neutrophils recruited to an aseptic inflammation in vivo were nonresponding. Superoxide production induced by Cmp1 was increased in latrunculin A-treated neutrophils, but no reactivation of desensitized FFA2R was induced by this drug, suggesting that the cytoskeleton is not directly involved in terminating the response. The functional and regulatory differences between the receptors that recognize short-chain fatty acids and formylated peptides, respectively, imply different roles of these receptors in the orchestration of inflammation and confirm the usefulness of a selective FFA2R agonist and antagonist as tools for the exploration of the precise role of the FFA2R.
authors: Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Lena
authors: L
authors: Björkman
authors: Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Jonas
authors: J
authors: Mårtensson
authors: Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Malene
authors: M
authors: Winther
authors: Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Michael
authors: M
authors: Gabl
authors: Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: André
authors: A
authors: Holdfeldt
authors: Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Martin
authors: M
authors: Uhrbom
authors: Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Department of Oral Microbiology and Immunology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Johan
authors: J
authors: Bylund
authors: University of Southern Denmark, Odense, Denmark.
authors: Anders
authors: A
authors: Højgaard Hansen
authors: University of Southern Denmark, Odense, Denmark.
authors: Sunil K
authors: SK
authors: Pandey
authors: University of Southern Denmark, Odense, Denmark.
authors: Trond
authors: T
authors: Ulven
authors: Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Huamei
authors: H
authors: Forsman
authors: Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Claes.Dahlgren@microbio.gu.se.
authors: Claes
authors: C
authors: Dahlgren
mesh_terms: D000085:Acetates / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled
chemical_list: D000085:Acetates; D002118:Calcium; D011956:Receptors, Cell Surface; D013481:Superoxides; D014409:Tumor Necrosis Factor-alpha; C473103:FFAR2 protein, human; D043562:Receptors, G-Protein-Coupled; C018824:ammonium acetate