Complement depletion enhances pulmonary inflammatory response after liver injury

Sean C. Glasgow, Sathyabama Kanakasabai, Sabarinathan Ramachandran, T. Mohanakumar, William C. Chapman

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Hepatic cryoablation can produce acute lung injury, with activation of nuclear factor (NF)-κB in the remnant liver and lungs, production of C-X-C chemokines, and neutrophil infiltration of the lungs. Activated complement stimulates NF-κB and cytokine secretion from Kupffer cells. The role of complement 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-κB-dependent promoter). Total complement depletion was achieved with preoperative administration of cobra venom factor (CVF). After hepatic cryoablation, bioluminescent NF-κB 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-κB 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 ± 29 versus 64 ± 13 pg/mg protein, P < 0.0001). Pulmonary myeloperoxidase activity was equivalent at 24 hours, but complement-depletion caused a significantly more rapid influx of neutrophils. Complement depletion results in increased pulmonary inflammation following liver cryo injury via relative upregulation of NF-κB activity. Activated complement is not the initiator of the systemic inflammatory response; in fact, downstream components of the complement cascade may diminish subsequent inflammation.

Original languageEnglish
Pages (from-to)357-364
Number of pages8
JournalJournal of Gastrointestinal Surgery
Volume10
Issue number3
DOIs
StatePublished - Mar 1 2006

Keywords

  • Acute lung injury
  • C3
  • CVF
  • Complement
  • Cryoablation

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