title: The roles of ribosomal protein S19 C-terminus in a shortened neutrophil lifespan through delta lactoferrin.
abstract: Cell lifespan is partially regulated by a balance between survival signals via constitutively active G protein-coupled receptors (GPCRs) and death signals via death receptors. We have demonstrated that neutrophils produce a mimic ligand of G protein-coupled C5a receptor (C5aR), ribosomal protein S19 (RP S19) polymer. In contrast to an original ligand C5a, RP S19 polymer induces not only inhibition of the guanine nucleotide exchange factor activity but also initiation of the regulator of G protein signaling 3 (RGS3) promoter in a RP S19 C-terminus dependent manner. To examine an antagonistic effect of the RP S19 C-terminus on G proteins, His-S-tagged C5a or C5a/RP S19, in which an RP S19 C-terminus is bound to the C5a C-terminus, was incubated with neutrophils, and a transcription factor delta lactoferrin (δLf) was identified as a specific binding protein via pull-down experiments. The S-tagged C5a-induced agonistic effects on chemotaxis, cytoplasmic Ca(2+) influx and p38 mitogen-activated protein kinase phosphorylation were not changed by Lf knockdown and δLf overexpression in neutrophil-like or macrophage-like cells, which were differentiated into mature cells from human promyelocytic leukemia HL-60 cells by dimethyl sulfoxide and phorbol-12-myristate-13-acetate, respectively. While, the S-tagged C5a/RP S19-induced antagonistic or agonistic effects on mature HL-60 neutrophil-like or macrophage-like cells were reversed by Lf knockdown and δLf overexpression, respectively. Moreover, RGS3 expression was increased in another HL-60 neutrophil-like cells under spontaneous apoptosis induced by an apoptotic inducer MnCl2. The RGS3 expression in apoptotic neutrophil-like cells was delayed not only by Lf knockdown but also by neutralization of the RP S19 polymer or C5aR. The inhibitory extension from G protein of C5aR to Gα subsets of constitutively active GPCRs along with the RP S19 polymer-induced translocation of δLf from the cytoplasmic face of the plasma membrane to the nucleus seems to shorten the neutrophil cell lifespan.
authors.affiliation: Division of Functional Pathology, Department of Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. Electronic address: hi-nishiura@hyo-med.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishiura
authors.affiliation: Division of Functional Pathology, Department of Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yamanegi
authors.affiliation: Division of Functional Pathology, Department of Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Mutsuki
authors.initials: M
authors.lastname: Kawabe
authors.affiliation: Division of Functional Pathology, Department of Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Nahoko
authors.initials: N
authors.lastname: Kato-Kogoe
authors.affiliation: Division of Functional Pathology, Department of Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Yamada
authors.affiliation: Division of Functional Pathology, Department of Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Nakasho
mesh_terms: D017209:Apoptosis / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002633:Chemotaxis / Q000276:immunology; D018922:HL-60 Cells; D006801:Humans; D017136:Ion Transport / Q000276:immunology; D007781:Lactoferrin / Q000235:genetics / Q000378:metabolism*; D008136:Longevity / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D010766:Phosphorylation; D020710:RGS Proteins / Q000096:biosynthesis*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012269:Ribosomal Proteins / Q000235:genetics*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C116760:GPRC5A protein, human; D020710:RGS Proteins; C485898:RGS3 protein, human; D043562:Receptors, G-Protein-Coupled; D012269:Ribosomal Proteins; C040343:ribosomal protein S19; D048051:p38 Mitogen-Activated Protein Kinases; D007781:Lactoferrin; D002118:Calcium
keywords: C5a receptor; Delta lactoferrin; Neutrophils; Regulator of G protein signaling 3; Ribosomal protein S19