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Macrophage alterations within the mesenteric lymphatic tissue are associated with impairment of lymphatic pump in metabolic syndrome
Author(s) -
Zawieja Scott D.,
Wang Wei,
Chakraborty Sanjukta,
Zawieja David C.,
Muthuchamy Mariappan
Publication year - 2016
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/micc.12307
Subject(s) - lymphatic system , macrophage polarization , cytokine , lymphatic endothelium , macrophage , medicine , chemokine , endocrinology , tumor necrosis factor alpha , biology , microbiology and biotechnology , immunology , inflammation , biochemistry , in vitro
Objective The intrinsic lymphatic pump is critical to proper lymph transport and is impaired in models of the MetSyn. Lymphatic contractile inhibition under inflammatory conditions has been linked with elevated NO production by activated myeloid–derived cells. Hence we hypothesized that inhibition of the MLV pump function in MetSyn animals was dependent on NO and was associated with altered macrophage recruitment and polarization within the MLV . Methods We used a high fructose‐fed rat model of MetSyn. Macrophage polarization was determined by whole mount immunofluorescence in mesenteric neurovascular bundles based on expression of CD 163, CD 206, and MHCII . We also utilized isolated vessel isobaric preparations to determine the role for elevated NO production in the inhibition of MLV contractility. Both LEC s and LMC s were used to assess the cytokines and chemokines to test how the lymphatic cells response to inflammatory conditions. Results Data demonstrated a greater accumulation of M1‐skewed ( CD 163 + MHCII + ) macrophages that were observed both within the perivascular adipose tissue and invested along the lymphatic vessels in MetSyn rats when compared to control rats. LEC s and LMC s basally express the macrophage maturation polarization cytokines monocyte colony‐stimulating factor and dramatically up regulate the M1 promoting cytokine granulocyte/monocyte colony‐stimulating factor in response to lipopolysaccharide stimulation. MetSyn MLV s exhibited altered phasic contraction frequency. Incubation of MetSyn MLV s with LNAME or Glib had a partial restoration of lymphatic contraction frequency. Conclusion The data presented here provide the first evidence for a correlation between alterations in macrophage status and lymphatic dysfunction that is partially mediated by NO and K ATP channel in MetSyn rats.