title: Macrophage alterations within the mesenteric lymphatic tissue are associated with impairment of lymphatic pump in metabolic syndrome.
abstract: 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.
  
  
  
  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 CD163, CD206, and MHCII. We also utilized isolated vessel isobaric preparations to determine the role for elevated NO production in the inhibition of MLV contractility. Both LECs and LMCs were used to assess the cytokines and chemokines to test how the lymphatic cells response to inflammatory conditions.
  
  
  
  Data demonstrated a greater accumulation of M1-skewed (CD163+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. LECs and LMCs 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 MLVs exhibited altered phasic contraction frequency. Incubation of MetSyn MLVs with LNAME or Glib had a partial restoration of lymphatic contraction frequency.
  
  
  
  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 KATPchannel in MetSyn rats.
authors: Department of Medical Physiology, College of Medicine, Cardiovascular Research Institute Division of Lymphatic Biology, Texas A&M Health Science Center, College Station, TX, USA.
authors: Scott D
authors: SD
authors: Zawieja
authors: Department of Medical Physiology, College of Medicine, Cardiovascular Research Institute Division of Lymphatic Biology, Texas A&M Health Science Center, College Station, TX, USA.
authors: Wei
authors: W
authors: Wang
authors: Department of Medical Physiology, College of Medicine, Cardiovascular Research Institute Division of Lymphatic Biology, Texas A&M Health Science Center, College Station, TX, USA.
authors: Sanjukta
authors: S
authors: Chakraborty
authors: Department of Medical Physiology, College of Medicine, Cardiovascular Research Institute Division of Lymphatic Biology, Texas A&M Health Science Center, College Station, TX, USA.
authors: David C
authors: DC
authors: Zawieja
authors: Department of Medical Physiology, College of Medicine, Cardiovascular Research Institute Division of Lymphatic Biology, Texas A&M Health Science Center, College Station, TX, USA. marim@tamu.edu.
authors: Mariappan
authors: M
authors: Muthuchamy
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D016130:Immunophenotyping; D037181:Lectins, C-Type / Q000032:analysis; D042601:Lymphatic Vessels / Q000502:physiology*; D008221:Lymphoid Tissue / Q000166:cytology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000032:analysis; D008643:Mesentery / Q000166:cytology*; D024821:Metabolic Syndrome / Q000276:immunology* / Q000503:physiopathology; D009119:Muscle Contraction / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000032:analysis; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D018925:Chemokines; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D009569:Nitric Oxide
keywords: lymphatic contractility; macrophage polarization; metabolic syndrome; nitric oxide