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Vascular Endothelial Cell Injury Partly Induced by Mesenteric Lymph in Heat Stroke

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Abstract

Animal models have shown that mesenteric lymph plays important roles in the pathogenesis of endothelium injury in many critical ill states. Gut-derived septicemia and endothelium injury are the two key pathogenesis of heat stroke (HS); however, it is unclear whether mesenteric lymph is cytotoxic to endothelium in HS. HS rat models were prepared in a prewarmed incubator. Mesenteric lymph, collected pre-, during, and post-HS, was analyzed for biological activity on human umbilical vein endothelial cell (HUVEC) in vitro. The effect of HS lymph on the production of von Willebrand factor (vWF), thrombomodulin (TM), and IL-6 by HUVEC was investigated. In vivo, vascular endothelium injury biomarkers, circulating endothelial cell (CEC), as well as serum soluble vWF and TM were tested in rats of HS and HS with mesenteric lymph duct ligation (HS-LDL). HS but not heat stroke sham mesenteric lymph-injured endothelial cells showed significantly increased HUVEC cytotoxicity and enhanced HUVEC monolayer permeability as well as elevated levels of vWF and TM production by HUVEC. IL-6 production by HUVEC was augmented by HS lymph in vitro. The effects of HS lymph on IL-6 production had a time course resembling that of the toxic effects of HS lymph on HUVEC. In vivo, when compared with HS rats, decreased CEC counts as well as lower serum vWF and TM concentrations were detected in HS-LDL rats. HS mesenteric lymph is probably harmful to vascular endothelium, which indicates that the modulation of mesenteric lymph may have some potential benefits to HS.

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REFERENCES

  1. Bouchama, A., and J.P. Knochel. 2002. Heat stroke. New England Journal of Medicine 346: 1978–1988.

    Article  CAS  PubMed  Google Scholar 

  2. Lu, K.C., J.Y. Wang, S.H. Lin, P. Chu, and Y.F. Lin. 2004. Role of circulating cytokines and chemokines in exertional heat stroke. Critical Care Medicine 32: 399–403.

    Article  CAS  PubMed  Google Scholar 

  3. Bouchama, A., V. Ollivier, G. Roberts, et al. 2005. Experimental heat stroke in baboon: Analysis of the systemic inflammatory response. Shock 24: 332–335.

    Article  CAS  PubMed  Google Scholar 

  4. Roberts, G.T., H. Ghebeh, M.A. Chishti, F. Al-Mohanna, R. El-Sayed, F. Al-Mohanna, and A. Bouchama. 2008. Microvascular injury, thrombosis, inflammation, and apoptosis in the pathogenesis of heat stroke: A study in baboon model. Arteriosclerosis, Thrombosis, and Vascular Biology 28: 1130–1136.

    Article  CAS  PubMed  Google Scholar 

  5. Lambert, G.P. 2009. Stress-induced gastrointestinal barrier dysfunction and its inflammatory effects. Journal of Animal Science 87: 101–108.

    Article  Google Scholar 

  6. Lambet, G.P. 2004. Role of gastrointestinal permeability in exertional heat stroke. American College of Sport Medicine 32: 185–190.

    Google Scholar 

  7. Gathiram, P., S.L. Gaffin, J.G. Brock-Utne, and M.T. Wells. 1987. Time course of endotoxemia and cardiovascular changes in heat-stressed primates. Aviation, Space, and Environmental Medicine 58: 1071–1074.

    CAS  PubMed  Google Scholar 

  8. Hall, D.M., G.R. Buettner, L.W. Oberley, L. Xu, R.D. Matthes, and C.V. Gisolfi. 2001. Mechanisms of circulatory and intestinal barrier dysfunction during whole body hyperthermia. American Journal of Physiology - Heart and Circulatory Physiology 280: 509–521.

    Article  Google Scholar 

  9. Selkirk, G.A., T.M. McLellan, H.E. Wright, and S.G. Rhind. 2008. Mild endotoxemia, NF-kappa B translocation, and cytokine increase during exertional heat stress in trained and untrained individuals. American Journal of Physiology - Regulatory, Integrative and Comparative Physiology 295: 611–623.

    Article  CAS  Google Scholar 

  10. Gathiram, P., M.T. Wells, D. Raidoo, J.G. Brock-utne, and S.L. Gaffin. 1988. Portal and systemic plasma lipopolysaccharide concentrations in heat-stressed primates. Circulatory Shock 25: 223–230.

    CAS  PubMed  Google Scholar 

  11. Deitch, E.A., R. Forsythe, D. Anjaria, D.H. Livingston, Q. Lu, D.Z. Xu, and H. Redl. 2004. The role of lymph factors in lung injury, bone marrow suppression and endothelial cell dysfunction in a primate model of trauma-hemorrhagic shock. Shock 22: 221–228.

    Article  PubMed  Google Scholar 

  12. Magnotti, L.J., J.S. Upperman, D.Z. Xu, Q. Lu, and E.A. Deitch. 1998. Gut-derived mesenteric lymph but not portal blood increases endothelial cell permeability and potentiates lung injury following hemorrhagic shock. Annals of Surgery 228: 518–527.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Chen, S.H., F.M. Chang, K.C. Niu, M.Y. Lin, and M.T. Lin. 2006. Resuscitation from experimental heat stroke by estrogen therapy. Critical Care Medicine 34(4): 1113–8.

    Article  CAS  PubMed  Google Scholar 

  14. Chen, S.H., F.M. Chang, H.K. Chang, W.C. Chen, K.F. Huang, and M.T. Lin. 2007. Human umbilical cord blood-derived CD34+ cells cause attenuation of multiorgan dysfunction during experimental heat stroke. Shock 27: 663–671.

    Article  CAS  PubMed  Google Scholar 

  15. Lee, J.J., M.T. Lin, N.L. Wang, C.L. Lin, and C.K. Chang. 2005. Platonin, a cyanine photosensitizing dye, causes attenuation of circulatory shock, hypercoagulable state, and tissue ischemia during heat stroke. Shock 24(6): 577–582.

    Article  PubMed  CAS  Google Scholar 

  16. Davidson, M.T., E.A. Deitch, Q. Lu, A. Osband, E. Feketeova, Z.H. Németh, G. Haskó, and D.Z. Xu. 2004. A study of the biologic activity of trauma-hemorrhagic shock mesenteric lymph over time and the relative role of cytokines. Surgery 136: 32–41.

    Article  PubMed  Google Scholar 

  17. Corwin, H.L., M.M. Schwartz, and E.J. Lewis. 1998. The importance of sample size in the interpretation of the renal biopsy. American Journal of Nephrology 8: 85–89.

    Article  Google Scholar 

  18. Iwata, Y., F. Kuzuya, M. Hayakawa, M. Naito, K. Shibata, and H. Endo. 1986. Circulating endothelial cells fail to induce cerebral infarction in rabbits. Stroke 17: 506–509.

    Article  CAS  PubMed  Google Scholar 

  19. Lambert, G.P., C.V. Gisolfi, D.J. Berg, P.L. Moseley, L.W. Oberley, and K.C. Kregel. 2002. Selected contribution: Hyperthermia-induced intestinal permeability and the role of oxidative and nitrosative stress. Journal of Applied Physiology 92: 1750–1761.

    Article  CAS  PubMed  Google Scholar 

  20. Bouchama, A., G. Roberts, F. Al Mohanna, R. El-Sayed, B. Lach, S. Chollet-Martin, V. Ollivier, R. Al Baradei, A. Loualich, S. Nakeeb, A. Eldali, and D. de Prost. 2005. Inflammatory, hemostatic, and clinical changes in a baboon experimental model for heat stroke. Journal of Applied Physiology 98: 697–705.

    Article  CAS  PubMed  Google Scholar 

  21. Gathiram, P., M.T. Wells, J.G. Brock-Utne, and S.L. Gaffin. 1987. Antilipopolysaccharide improves survival in primates subjected to heat stroke. Circulatory Shock 23: 157–164.

    CAS  PubMed  Google Scholar 

  22. Gathiram, P., M.T. Wells, J.G. Brock-Utne, B.C. Wessels, and S.L. Gaffin. 1988. Oral administered nonabsorbable antibiotics prevent endotoxemia in primates following intestinal ischemia. Journal of Surgical Research 45: 187–193.

    Article  CAS  PubMed  Google Scholar 

  23. Bouchama, A., M.M. Hammami, A. Haq, J. Jackson, and S. al-Sedairy. 1996. Evidence for endothelial cell activation/injury in heat stroke. Critical Care Medicine 24: 1173–1178.

    Article  CAS  PubMed  Google Scholar 

  24. Deitch, E.A. 2001. Role of the gut lymphatic system in multiple organ failure. Current Opinion in Critical Care 7: 92–8.

    Article  CAS  PubMed  Google Scholar 

  25. Fanous, M.Y., A.J. Phillips, and J.A. Windsor. 2007. Mesenteric lymph: the bridge to future management of critical illness. Journal of the Pancreas 8: 374–399.

    PubMed  Google Scholar 

  26. Deitch, E.A. 2010. Gut lymph and lymphatics: A source of factors leading to organ injury and dysfunction. Annals of the New York Academy of Sciences 1207: 103–111.

    Article  Google Scholar 

  27. Niu, C.Y., Y.L. Hou, Z.G. Zhao, Y.F. Zhang, J.J. Ji, H.X. Qiao, J. Zhang, and Y.M. Yao. 2007. Role of intestinal lymphatic pathway in pathogenesis of intestine-derived bacteria/endotoxin translocation in rats in shock. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 19: 266–9.

    CAS  PubMed  Google Scholar 

  28. Ang, C., and J. Dawes. 1994. The effects of hyperthermia on human endothelial monolayers: Modulation of thrombotic potential and permeability. Blood Coagulation & Fibrinolysis 5: 193–9.

    Article  CAS  Google Scholar 

  29. Hammami, M.M., A. Bouchama, E. Shail, H.Y. Aboul-Enein, and S. Al-Sedairy. 1998. Lymphocyte subsets and adhesion molecules expression in heat stroke and heat stress. Journal of Applied Physiology 84: 1615–21.

    Article  CAS  PubMed  Google Scholar 

  30. Park, K.J., S.H. Kang, Y.S. Chae, M.O. Yu, T.H. Cho, J.K. Suh, H.K. Lee, and Y.G. Chung. 2010. Influence of interleukin-6 on the development of peritumoral brain edema in meningiomas. Journal of Neurosurgery 112: 73–80.

    Article  CAS  PubMed  Google Scholar 

  31. Kaplanski, G., V. Marin, F. Montero-Julian, A. Mantovani, and C. Farnarier. 2003. IL-6: a regulator of the transition from neutrophil to monocyte recruitment during inflammation. Trends in Immunology 24: 25–29.

    Article  CAS  PubMed  Google Scholar 

  32. Hall, D.M., K.R. Baumgardner, T.D. Oberley, and C.V. Gisolfi. 1999. Splanchnic tissues undergo hypoxic stress during whole body hyperthermia. American Journal of Physiology 276: 1195–203.

    Google Scholar 

  33. Lambert, G.P. 2008. Intestinal barrier dysfunction, endotoxemia, and gastrointestinal symptoms: The ‘canary in the coal mine’ during exercise-heat stress? Medicine and Sport Science 53: 61–73.

    Article  PubMed  Google Scholar 

  34. Deitch, E.A., H.P. Shi, Q. Lu, E. Feketeova, and D.Z. Xu. 2003. Serine proteases are involved in the pathogenesis of trauma-hemorrhagic shock-induced gut and lung injury. Shock 19: 452–6.

    Article  CAS  PubMed  Google Scholar 

  35. Gonzalez, R.J., E.E. Moore, D.J. Ciesla, X. Meng, W.L. Biffl, and C.C. Silliman. 2001. Post-hemorrhagic shock mesenteric lymph lipids prime neutrophils for enhanced cytotoxicity via phospholipase A2. Shock. 16: 218–22.

    Article  CAS  PubMed  Google Scholar 

  36. Gonzalez, R.J., E.E. Moore, D.J. Ciesla, W.L. Biffl, P.J. Offner, and C.C. Silliman. 2001. Phospholipase A(2). Derived neutral lipids from posthemorrhagic shock mesenteric lymph prime the neutrophil oxidative burst. Surgery 130: 198–203.

    Article  CAS  PubMed  Google Scholar 

  37. Davidson, M.T., E.A. Deitch, Q. Lu, G. Haskó, B. Abungu, Z.H. Németh, S.B. Zaets, L.D. Gaspers, A.P. Thomas, and D.Z. Xu. 2004. Trauma-hemorrhagic shock mesenteric lymph induces endothelial apoptosis that involves both caspase-dependent and caspase-independent mechanisms. Annals of Surgery 240: 123–31.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Gonzalez, R.J., E.E. Moore, W.L. Biffl, D.J. Ciesla, and C.C. Silliman. 2000. The lipid fraction of post-hemorrhagic shock mesenteric lymph (PHSML) inhibits neutrophil apoptosis and enhances cytotoxic potential. Shock 14: 404–408.

    Article  CAS  PubMed  Google Scholar 

  39. Sarin, E.L., E.E. Moore, J.B. Moore, T. Masuno, J.L. Moore, A. Banerjee, and C.C. Silliman. 2004. Systemic neutrophil priming by lipid mediators in post-shock mesenteric lymph exists across species. Journal of Traumatology 57: 950–954.

    Google Scholar 

  40. Dayal, S.D., C.J. Hauser, E. Feketeova, Z. Fekete, J.M. Adams, Q. Lu, D.Z. Xu, S. Zaets, and E.A. Deitch. 2002. Shock mesenteric lymph induced rat polymorphonuclear neutrophil activation and endothelial cell injury is mediated by aqueous factors. Journal of Traumatology 52: 1048–1055.

    Google Scholar 

  41. Kaiser, V.L., Z.C. Sifri, G.S. Dikdan, T. Berezina, S. Zaets, Q. Lu, D.Z. Xu, and E.A. Deitch. 2005. Trauma-hemorrhagic shock mesenteric lymph from the rat contains a modified form of albumin that is implicated in endothelial cell toxicity. Shock 23: 417–425.

    Article  CAS  PubMed  Google Scholar 

  42. Haubitz, M., and A. Woywodt. 2004. Circulating endothelial cells and vasculitis. Internal Medicine 43: 660–667.

    Article  CAS  PubMed  Google Scholar 

  43. Mutunga, M., B. Fulton, R. Bullock, A. Batchelor, A. Gascoigne, J.I. Gillespie, and S.V. Baudouin. 2001. Circulating endothelial cells in patients with septic shock. American Journal of Respiratory and Critical Care Medicine 163: 195–200.

    Article  CAS  PubMed  Google Scholar 

  44. Lee, K.W., G.Y. Lip, M. Tayebjee, W. Foster, and A.D. Blann. 2005. Circulating endothelial cells, von Willebrand factor, interleukin-6, and prognosis in patients with acute coronary syndromes. Blood 105: 526–532.

    Article  CAS  PubMed  Google Scholar 

  45. Nakayama, T., W. Sato, A. Yoshimura, L. Zhang, T. Kosugi, M. Campbell-Thompson, H. Kojima, B.P. Croker, and T. Nakagawa. 2010. Endothelial von Willebrand factor release due to eNOS deficiency predisposes to thrombotic microangiopathy in mouse aging kidney. American Journal of Pathology 176: 2198–2208.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Hagiwara, S., H. Iwasaka, K. Goto, Y. Ochi, S. Mizunaga, T. Saikawa, and T. Noguchi. 2010. Recombinant thrombomodulin prevents heat stroke by inhibition of high-mobility group box 1 protein in sera of rats. Shock 34: 402–406.

    Article  CAS  PubMed  Google Scholar 

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ACKNOWLEDGMENTS

This work is supported by the National Natural Science Foundation of China (project 81101406) and Medical Research of PLA (project BWS12J108).

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  1. Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China

    HuaSheng Tong, Peng Wan, XingQin Zhang, PengKai Duan, YouQing Tang, Yi Chen, LiQun Tang & Lei Su

  2. Key Laboratory of Tropical Zone Trauma Care and Tissue Repair of PLA, Guangzhou, China

    HuaSheng Tong, Peng Wan, XingQin Zhang, PengKai Duan, YouQing Tang, Yi Chen, LiQun Tang & Lei Su

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Tong, H., Wan, P., Zhang, X. et al. Vascular Endothelial Cell Injury Partly Induced by Mesenteric Lymph in Heat Stroke. Inflammation 37, 27–34 (2014). https://doi.org/10.1007/s10753-013-9708-x

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