Journal
TRANSPLANTATION
Volume 84, Issue 8, Pages 1012-1019Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.tp.0000286040.85007.89
Keywords
bronchiolitis obliterans; allograft rejection; innate immunity; toll-like receptor-4.
Categories
Funding
- Intramural NIH HHS Funding Source: Medline
- NHLBI NIH HHS [P50HL-084917, K23 HL069978, HL69978, P50 HL084917] Funding Source: Medline
Ask authors/readers for more resources
Background. Alloimmune lung injury, characterized by perivascular lymphocytic inflammation, lymphocytic bronchiolitis (LB), and obliterative bronchiolitis (OB), causes substantial morbidity and mortality after lung transplantation and bone marrow transplantation (BMT), but little is known regarding its pathogenesis. We have developed and pursued the hypothesis that local activation of pulmonary innate immunity through toll-like receptor (TLR)-4 is critical to the development of posttransplant alloimmune lung injury. Methods. We developed a fully major histocompatibility complex-mismatched murine BMT model without systemic graft-versus-host disease, and challenged mice with aerosolized lipopolysaccharide (LPS), a prototypic TLR4 agonist, to determine the effect upon pulmonary alloimmune lung injury. Results. LPS-exposed allogeneic BMT recipient mice developed histological and biological features of LB and 013, which were not observed in non-LPS-exposed allogeneic controls or syngeneic LPS-exposed mice. LPS-induced lymphocytic lung inflammation was dependent upon intact TLR4 signaling in donor-derived hematopoietic cells but not recipient structural lung cells, demonstrating a distinct function for TLR4 on hematopoietic cells in mediating alloimmunity. Conclusions. We demonstrate a critical role for localized, environmentally induced innate immune activation in promoting alloimmune lung injury. Local inhibition of TLR4 signaling in pulmonary resident
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available