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Complement depletion enhances pulmonary inflammatory response after liver injury

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Journal of Gastrointestinal Surgery Aims and scope

Abstract

Hepatic cryoablation can produce acute lung injury, with activation of nuclear factor (NF)-кB in the remnant liver and lungs, production of C-X-C chemokines, and neutrophil infiltration of the lungs. Ac-tivated complement stimulates NF-к B and cytokine secretion from Kupffer cells. The role of comple-ment in the development of acute lung injury after cryoablation was examined using HLL transgenic mice (5’ HIV-LTR-Luciferase gene; 5’ HIV-LTR is an NF-к B-dependent promoter). Total comple-ment depletion was achieved with preoperative administration of cobra venom factor (CVF). After he-patic cryoablation, bioluminescent NF-кB activity increased in the nonablated liver remnant by 4 hours in both control (119,093 ± 22,808 net RLU/mg protein) and CVF-treated mice (117,722 ± 14,932) from cumulative baseline (657 ± 90, P < 0.0001). In the lung, complement-depletion induced significantly greater increases in NF-к B activation at both early and later times. Likewise, chemokines were higher in complement-depleted mice relative to controls (KC: 493 ± 43 versus 269 ± 29 pg/mg protein, P < 0.001; MIP-2: 171 6 29 versus 64 6 13 pg/mg protein, P < 0.0001). Pulmonary myelo-peroxidase activity was equivalent at 24 hours, but complement-depletion caused a significantly more rapid influx of neutrophils. Complement depletion results in increased pulmonary inflammation follow-ing liver cryo injury via relative upregulation of NF-к B activity. Activated complement is not the initiator of the systemic inflammatory response; in fact, downstream components of the complement cascade may diminish subsequent inflammation.

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Authors and Affiliations

  1. Department of Surgery, Washington University, St. Louis, Missouri

    Sean C. Glasgow M.D., Sathyabama Kanakasabai M.D., Sabarinathan Ramachandran Ph.D., T. Mohanakumar Ph.D. & William C. Chapman M.D.

  2. Section of Abdominal Transplantation, and the Department of Pathology and Immunology, Washington University, St. Louis, Missouri

    T. Mohanakumar Ph.D.

Authors
  1. Sean C. Glasgow M.D.
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  2. Sathyabama Kanakasabai M.D.
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  3. Sabarinathan Ramachandran Ph.D.
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  4. T. Mohanakumar Ph.D.
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  5. William C. Chapman M.D.
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Correspondence to William C. Chapman M.D..

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Glasgow, S.C., Kanakasabai, S., Ramachandran, S. et al. Complement depletion enhances pulmonary inflammatory response after liver injury. J Gastrointest Surg 10, 357–364 (2006). https://doi.org/10.1016/j.gassur.2005.06.033

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  • DOI: https://doi.org/10.1016/j.gassur.2005.06.033

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