title: Effect of TREM-1 blockade and single nucleotide variants in experimental renal injury and kidney transplantation.
abstract: Renal ischemia reperfusion (IR)-injury induces activation of innate immune response which sustains renal injury and contributes to the development of delayed graft function (DGF). Triggering receptor expressed on myeloid cells-1 (TREM-1) is a pro-inflammatory evolutionary conserved pattern recognition receptor expressed on a variety of innate immune cells. TREM-1 expression increases following acute and chronic renal injury. However, the function of TREM-1 in renal IR is still unclear. Here, we investigated expression and function of TREM-1 in a murine model of renal IR using different TREM-1 inhibitors: LP17, LR12 and TREM-1 fusion protein. In a human study, we analyzed the association of non-synonymous single nucleotide variants in the TREM1 gene in a cohort comprising 1263 matching donors and recipients with post-transplant outcomes, including DGF. Our findings demonstrated that, following murine IR, renal TREM-1 expression increased due to the influx of Trem1 mRNA expressing cells detected by in situ hybridization. However, TREM-1 interventions by means of LP17, LR12 and TREM-1 fusion protein did not ameliorate IR-induced injury. In the human renal transplant cohort, donor and recipient TREM1 gene variant p.Thr25Ser was not associated with DGF, nor with biopsy-proven rejection or death-censored graft failure. We conclude that TREM-1 does not play a major role during experimental renal IR and after kidney transplantation.
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tammaro
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Jesper
authors.initials: J
authors.lastname: Kers
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Diba
authors.initials: D
authors.lastname: Emal
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Stroo
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Gwendoline J D
authors.initials: GJD
authors.lastname: Teske
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Loes M
authors.initials: LM
authors.lastname: Butter
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Nike
authors.initials: N
authors.lastname: Claessen
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Damman
authors.affiliation: Inserm UMR_S1116, Faculté de Médecine de Nancy, Université de Lorraine, Vandoeuvre-les-Nancy, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Derive
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Gerjan J
authors.initials: GJ
authors.lastname: Navis
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Department of Pathology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Jaklien C
authors.initials: JC
authors.lastname: Leemans
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Dessing
mesh_terms: D000818:Animals; D051799:Delayed Graft Function / Q000235:genetics* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects; D007850:Lauric Acids / Q000008:administration & dosage; D051379:Mice; D009842:Oligopeptides; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D012235:Rhodamines / Q000008:administration & dosage; D000073871:Triggering Receptor Expressed on Myeloid Cells-1 / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D007850:Lauric Acids; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; D012235:Rhodamines; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; C420324:nangibotide