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Role of complement activation in obliterative bronchiolitis post-lung transplantation.

Publication ,  Journal Article
Suzuki, H; Lasbury, ME; Fan, L; Vittal, R; Mickler, EA; Benson, HL; Shilling, R; Wu, Q; Weber, DJ; Wagner, SR; Lasaro, M; Devore, D; Wang, Y ...
Published in: J Immunol
October 15, 2013

Obliterative bronchiolitis (OB) post-lung transplantation involves IL-17-regulated autoimmunity to type V collagen and alloimmunity, which could be enhanced by complement activation. However, the specific role of complement activation in lung allograft pathology, IL-17 production, and OB is unknown. The current study examines the role of complement activation in OB. Complement-regulatory protein (CRP) (CD55, CD46, complement receptor 1-related protein y/CD46) expression was downregulated in human and murine OB; and C3a, a marker of complement activation, was upregulated locally. IL-17 differentially suppressed complement receptor 1-related protein y expression in airway epithelial cells in vitro. Neutralizing IL-17 recovered CRP expression in murine lung allografts and decreased local C3a production. Exogenous C3a enhanced IL-17 production from alloantigen- or autoantigen (type V collagen)-reactive lymphocytes. Systemically neutralizing C5 abrogated the development of OB, reduced acute rejection severity, lowered systemic and local levels of C3a and C5a, recovered CRP expression, and diminished systemic IL-17 and IL-6 levels. These data indicated that OB induction is in part complement dependent due to IL-17-mediated downregulation of CRPs on airway epithelium. C3a and IL-17 are part of a feed-forward loop that may enhance CRP downregulation, suggesting that complement blockade could be a therapeutic strategy for OB.

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Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

October 15, 2013

Volume

191

Issue

8

Start / End Page

4431 / 4439

Location

United States

Related Subject Headings

  • Receptors, Complement 3b
  • Receptors, Complement
  • Mice, Inbred C57BL
  • Mice
  • Membrane Cofactor Protein
  • Lymphocyte Culture Test, Mixed
  • Lung Transplantation
  • Interleukin-6
  • Interleukin-17
  • Immunology
 

Citation

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Suzuki, H., Lasbury, M. E., Fan, L., Vittal, R., Mickler, E. A., Benson, H. L., … Wilkes, D. S. (2013). Role of complement activation in obliterative bronchiolitis post-lung transplantation. J Immunol, 191(8), 4431–4439. https://doi.org/10.4049/jimmunol.1202242
Suzuki, Hidemi, Mark E. Lasbury, Lin Fan, Ragini Vittal, Elizabeth A. Mickler, Heather L. Benson, Rebecca Shilling, et al. “Role of complement activation in obliterative bronchiolitis post-lung transplantation.J Immunol 191, no. 8 (October 15, 2013): 4431–39. https://doi.org/10.4049/jimmunol.1202242.
Suzuki H, Lasbury ME, Fan L, Vittal R, Mickler EA, Benson HL, et al. Role of complement activation in obliterative bronchiolitis post-lung transplantation. J Immunol. 2013 Oct 15;191(8):4431–9.
Suzuki, Hidemi, et al. “Role of complement activation in obliterative bronchiolitis post-lung transplantation.J Immunol, vol. 191, no. 8, Oct. 2013, pp. 4431–39. Pubmed, doi:10.4049/jimmunol.1202242.
Suzuki H, Lasbury ME, Fan L, Vittal R, Mickler EA, Benson HL, Shilling R, Wu Q, Weber DJ, Wagner SR, Lasaro M, Devore D, Wang Y, Sandusky GE, Lipking K, Pandya P, Reynolds J, Love R, Wozniak T, Gu H, Brown KM, Wilkes DS. Role of complement activation in obliterative bronchiolitis post-lung transplantation. J Immunol. 2013 Oct 15;191(8):4431–4439.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

October 15, 2013

Volume

191

Issue

8

Start / End Page

4431 / 4439

Location

United States

Related Subject Headings

  • Receptors, Complement 3b
  • Receptors, Complement
  • Mice, Inbred C57BL
  • Mice
  • Membrane Cofactor Protein
  • Lymphocyte Culture Test, Mixed
  • Lung Transplantation
  • Interleukin-6
  • Interleukin-17
  • Immunology