title: Involvement of proteinase-activated receptors 1 and 2 in spreading and phagocytosis by murine adherent peritoneal cells: modulation by the C-terminal of S100A9 protein.
abstract: Proteinase-activated receptors (PAR) are widely recognized for their modulatory properties in inflammatory and immune responses; however, their direct role on phagocyte effector functions remains unknown. S100A9, a protein secreted during inflammatory responses, deactivates activated peritoneal macrophages, and its C-terminal portion inhibits spreading and phagocytosis of adherent peritoneal cells. Herein, the effect of PAR1 and PAR2 agonists was investigated on spreading and phagocytosis by adherent peritoneal cells, as well as the ability of murine C-terminal of S100A9 peptide (mS100A9p) to modulate this effect. Adherent peritoneal cells obtained from mouse abdominal cavity were incubated with PAR1 and PAR2 agonists and spreading and phagocytosis of Candida albicans particles were evaluated. PAR1 agonists increased both the spreading and the phagocytic activity, but PAR2 agonists only increased the spreading index. mS100A9p reverted both the increased spreading and phagocytosis induced by PAR1 agonists, but no interference in the increased spreading induced by PAR2 agonists was noticed. The shorter homologue peptide to the C-terminal of mS100A9p, corresponding to the H(92)-E(97) region, also reverted the increased spreading and phagocytosis induced by PAR1 agonists. These findings show that proteinase-activated receptors have an important role for spreading and phagocytosis of adherent peritoneal cells, and that the peptide corresponding to the C-terminal of S100A9 protein is a remarkable candidate for use as a novel compound to modulate PAR1 function.
authors: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av Prof Lineu Prestes, São Paulo, SP, Brazil.
authors: Rosana L
authors: RL
authors: Pagano
authors: Sandra C
authors: SC
authors: Sampaio
authors: Maria A
authors: MA
authors: Juliano
authors: Luiz
authors: L
authors: Juliano
authors: Renata
authors: R
authors: Giorgi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D040502:Calgranulin B / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D002448:Cell Adhesion; D048430:Cell Shape / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010537:Peritoneum / Q000166:cytology* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D044463:Receptor, PAR-1 / Q000819:agonists / Q000737:chemistry / Q000378:metabolism*; D044464:Receptor, PAR-2 / Q000819:agonists / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015032:Zinc / Q000378:metabolism
chemical_list: D040502:Calgranulin B; D010446:Peptide Fragments; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D015032:Zinc