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LPS mediated decreases in immune cells recruitment on or near lymphatics impairs lymphatic contractility
Author(s) -
Chakraborty Sanjukta,
Zawieja David C,
Muthuchamy Mariappan
Publication year - 2013
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.27.1_supplement.681.5
Subject(s) - lymphatic system , immune system , contractility , inflammation , lipopolysaccharide , proinflammatory cytokine , chemokine , lymphatic endothelium , immunology , biology , chemistry , endocrinology
Elevated levels of dietary endotoxins like lipopolysaccharide (LPS) are linked to several chronic inflammatory pathologies involving the lymphatics. However, the mechanisms of LPS modulated changes in lymphatic contractility have not been understood. Our hypothesis is that LPS mediated inflammation modulates the immune cell populations on or in vicinity of the lymphatics, resulting in changes in cytokines and chemokines that impair lymphatic function. To demonstrate this, rats were injected with LPS, and immune cells (eosinophils, neutrophils, macrophages and monocytes) were detected by confocal microscopy after 6hr, 24hr and 3d in whole mount mesenteric lymphatic preparations. We found a significant reduction in eosinophils and neutrophils 3d post LPS treatment and an increase in macrophages and monocytes. Treatment of lymphatic muscle cells with some of the key cytokines released by these cells (IL4, IL13, IL5 and IL8) showed an increase in relative levels of myosin light chain 20 phosphorylation by activation of AKT and ERK1/2. These cytokines also mitigated LPS induced impairment of lymphatic contractility in a time‐dependent manner. Together, our data show that LPS impairs lymphatic function by decreasing neutrophils and eosinophils on/near lymphatic vessels, thereby reducing the availability of key cytokines and their effects on lymphatic muscle. AHA 09POST2280005 to SC; KO2 HL86650 to MM