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Mast Cells‐Dependent Compromised Response of Aged Mesenteric Lymphatic Vessels and Surrounding Tissues to the Acute Inflammatory Challenge
Author(s) -
Skoog Hunter,
Dusio Giuseppina F.,
Tobin Richard,
Zawieja David C.,
NewellRogers M. Karen,
Gashev Anatoliy A.,
Nizamutdinova Irina Tsoy
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.726.6
Subject(s) - lymphatic system , inflammation , medicine , degranulation , mast cell , lipopolysaccharide , pathology , mesenteric lymph nodes , immunology , immune system , receptor
Mesenteric lymphatic vessels (MLVs), being located at the border between the biologically aggressive environment of the gut lumen and inner compartments of the abdomen have not been studied in depth as an active component of the anti‐inflammatory defense system of the body. Aging creates several challenges for lymphatic vessels by altering their ultrastructure, contractility and consequently lymph flow as well as their microenvironment. We found an increase in number and degree of basal activation of mast cells (MC) nearby aged mesenteric lymphatic vessels. Such, as we predicted, will delimit ability of aged mesenteric tissue to respond to acute inflammatory challenge. In current study we attempted to establish mechanistic links between the aging‐associated changes in functional status of MCs and the altered responses of mesenteric tissue and MLVs to acute inflammatory insult. We used in vivo model of induction of acute peritoneal inflammation by lipopolysaccharide (LPS) treatment (24 hours after single IP injection of LPS in dose of 10 mg/kg body weight into adult (9‐mo) and aged (24‐mo) F‐344 rats). Analysis of data obtained by studies based on ruthenium red staining of MCs and by flow cytometry‐based measurements demonstrate that LPS‐induced degranulation of MCs in aged mesentery is greatly diminished. Latter co‐exists with basal activation of NF‐κB signaling in aged MLVs and mesenteric tissue therefore additional LPS‐induced NF‐κB activation is also reduced. Furthermore both mast cell stabilization by Cromolyn, or application of mixture of Histamine H1–H4 receptor blockers, are able to prevent the NF‐κB activation in mesentery/MLVs. NF‐κB, as hallmark of aging‐associated low‐grade inflammation, controls the release of pro‐inflammatory cytokines. To identify the corresponding aging‐associated differences, 24 hours after LPS injection we compared blood and mesenteric tissue (including MLVs) samples from adult and aged rats for 27 major pro‐inflammatory cytokines, using a Multiplex cytokine assay system (kit RECMAG65K27PMX, Millipore, US). The obtained results show that there is an elevation of NF‐κB‐dependent pro‐inflammatory cytokines in aged mesentery/MLVs with imbalance of Th1/Th2 cytokine profile and subsequent changes in T and B cells populations. Cumulatively, our data indicate that pre‐existing activation of MCs in aged mesentery by MLVs linked to its altered response to LPS, associated with histamine/NF‐κB‐dependent specific changes in cytokine levels. Latter can contribute to imbalance of immune cells profile and decreased ability of the aged immune system to respond to acute inflammatory challenge in peritoneal compartment of the body. Support or Funding Information NIH/NIDDK 1R56DK099161