title: Mast cells and histamine are triggering the NF-κB-mediated reactions of adult and aged perilymphatic mesenteric tissues to acute inflammation.
abstract: This study aimed to establish mechanistic links between the aging-associated changes in the functional status of mast cells and the altered responses of mesenteric tissue and mesenteric lymphatic vessels (MLVs) to acute inflammation. We used anin vivomodel of acute peritoneal inflammation induced by lipopolysaccharide treatment of adult (9-month) and aged (24-month) F-344 rats. We analyzed contractility of isolated MLVs, mast cell activation, activation of nuclear factor-κB (NF-κB) without and with stabilization of mast cells by cromolyn or blockade of all types of histamine receptors and production of 27 major pro-inflammatory cytokines in adult and aged perilymphatic mesenteric tissues and blood. We found that the reactivity of aged contracting lymphatic vessels to LPS-induced acute inflammation was abolished and that activated mast cells trigger NF-κB signaling in the mesentery through release of histamine. The aging-associated basal activation of mesenteric mast cells limits acute inflammatory NF-κB activation in aged mesentery. We conclude that proper functioning of the mast cell/histamine/NF-κB axis is necessary for reactions of the lymphatic vessels to acute inflammatory stimuli as well as for interaction and trafficking of immune cells near and within the collecting lymphatics.
authors.affiliation: Department of Medical Physiology, College of Medicine, Texas A&M University Health Science Center, Temple, TX 76504, USA.
authors.forename: Irina Tsoy
authors.initials: IT
authors.lastname: Nizamutdinova
authors.affiliation: Department of Surgery, Baylor Scott and White Health, Texas A&M University Health Science Center, Temple, TX 76504, USA.
authors.forename: Giuseppina F
authors.initials: GF
authors.lastname: Dusio
authors.affiliation: Department of Medical Physiology, College of Medicine, Texas A&M University Health Science Center, Temple, TX 76504, USA.
authors.forename: Olga Yu
authors.initials: OY
authors.lastname: Gasheva
authors.affiliation: Department of Medical Physiology, College of Medicine, Texas A&M University Health Science Center, Temple, TX 76504, USA.
authors.forename: Hunter
authors.initials: H
authors.lastname: Skoog
authors.affiliation: Department of Surgery, Baylor Scott and White Health, Texas A&M University Health Science Center, Temple, TX 76504, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Tobin
authors.affiliation: Department of Surgery, Baylor Scott and White Health, Texas A&M University Health Science Center, Temple, TX 76504, USA.
authors.forename: Chander
authors.initials: C
authors.lastname: Peddaboina
authors.affiliation: Department of Medical Physiology, College of Medicine, Texas A&M University Health Science Center, Temple, TX 76504, USA.
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Meininger
authors.affiliation: Department of Medical Physiology, College of Medicine, Texas A&M University Health Science Center, Temple, TX 76504, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Zawieja
authors.affiliation: Department of Surgery, Baylor Scott and White Health, Texas A&M University Health Science Center, Temple, TX 76504, USA.
authors.forename: M Karen
authors.initials: MK
authors.lastname: Newell-Rogers
authors.affiliation: Department of Medical Physiology, College of Medicine, Texas A&M University Health Science Center, Temple, TX 76504, USA.
authors.forename: Anatoliy A
authors.initials: AA
authors.lastname: Gashev
mesh_terms: D000818:Animals; D004205:Cromolyn Sodium / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D042601:Lymphatic Vessels / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D008643:Mesentery / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010532:Peritoneal Diseases / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D006632:Histamine; D004205:Cromolyn Sodium
keywords: NF-κB signaling; aging; histamine; lymphatic vessel; mast cell