Role of Complement Activation in Obliterative Bronchiolitis Post-Lung Transplantation.

Role of Complement Activation in Obliterative Bronchiolitis Post-Lung Transplantation. J Immunol. 2013 Sep 16; Authors: 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 Abstract 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 system...
Source: Journal of Immunology - Category: Allergy & Immunology Authors: Tags: J Immunol Source Type: research