Lipopolysaccharide modulates neutrophil recruitment and macrophage polarization on lymphatic vessels and impairs lymphatic function in rat mesentery.

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  • Additional Information
    • Source:
      Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901228 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1539 (Electronic) Linking ISSN: 03636135 NLM ISO Abbreviation: Am J Physiol Heart Circ Physiol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Bethesda, Md. : American Physiological Society,
    • Subject Terms:
      Cell Polarity/*drug effects ; Lipopolysaccharides/*pharmacology ; Lymphatic Diseases/*chemically induced ; Lymphatic Vessels/*drug effects ; Macrophages/*drug effects ; Mesentery/*pathology ; Neutrophil Infiltration/*drug effects; Animals ; Cell Adhesion Molecules/metabolism ; Chemokines/biosynthesis ; Cytokines/biosynthesis ; Immunity, Innate/drug effects ; In Vitro Techniques ; Inflammation/chemically induced ; Inflammation/pathology ; Lymphatic Diseases/pathology ; Lymphatic Vessels/cytology ; MAP Kinase Signaling System/drug effects ; Male ; Muscle Contraction/drug effects ; Muscle, Smooth, Vascular/pathology ; Rats ; Rats, Sprague-Dawley
    • Abstract:
      Impairment of the lymphatic system is apparent in multiple inflammatory pathologies connected to elevated endotoxins such as LPS. However, the direct mechanisms by which LPS influences the lymphatic contractility are not well understood. We hypothesized that a dynamic modulation of innate immune cell populations in mesentery under inflammatory conditions perturbs tissue cytokine/chemokine homeostasis and subsequently influences lymphatic function. We used rats that were intraperitoneally injected with LPS (10 mg/kg) to determine the changes in the profiles of innate immune cells in the mesentery and in the stretch-mediated contractile responses of isolated lymphatic preparations. Results demonstrated a reduction in the phasic contractile activity of mesenteric lymphatic vessels from LPS-injected rats and a severe impairment of lymphatic pump function and flow. There was a significant reduction in the number of neutrophils and an increase in monocytes/macrophages present on the lymphatic vessels and in the clear mesentery of the LPS group. This population of monocytes and macrophages established a robust M2 phenotype, with the majority showing high expression of CD163 and CD206. Several cytokines and chemoattractants for neutrophils and macrophages were significantly changed in the mesentery of LPS-injected rats. Treatment of lymphatic muscle cells (LMCs) with LPS showed significant changes in the expression of adhesion molecules, VCAM1, ICAM1, CXCR2, and galectin-9. LPS-TLR4-mediated regulation of pAKT, pERK pI-κB, and pMLC20 in LMCs promoted both contractile and inflammatory pathways. Thus, our data provide the first evidence connecting the dynamic changes in innate immune cells on or near the lymphatics and complex cytokine milieu during inflammation with lymphatic dysfunction.
      (Copyright © 2015 the American Physiological Society.)
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    • Grant Information:
      R01 DK099221 United States DK NIDDK NIH HHS; R01-DK-99221 United States DK NIDDK NIH HHS
    • Contributed Indexing:
      Keywords: M1 and M2 macrophages; inflammation; lipopolysaccharide; lymphatic function; neutrophils
    • Accession Number:
      0 (Cell Adhesion Molecules)
      0 (Chemokines)
      0 (Cytokines)
      0 (Lipopolysaccharides)
    • Publication Date:
      Date Created: 20151011 Date Completed: 20160411 Latest Revision: 20200930
    • Publication Date:
      20240829
    • Accession Number:
      PMC4698422
    • Accession Number:
      10.1152/ajpheart.00467.2015
    • Accession Number:
      26453331