Hyaluronan contributes to bronchiolitis obliterans syndrome and stimulates lung allograft rejection through activation of innate immunity.

摘要: Rationale: Although innate immunity is increasingly recognized to contribute lung allograft rejection, the significance of endogenous ligands, such as hyaluronan (HA) fragments, in clinical or experimental transplantation uncertain. Objectives: To determine if HA associated with bronchiolitis obliterans syndrome (BOS) transplant recipients, and evaluate effect low- high-molecular-weight on including dependence signaling pathways effector cells. Methods: concentrations were measured bronchoalveolar lavage plasma samples from recipients without established BOS. BOS normal tissues assessed for localization expression synthases. Murine orthotopic tolerance treated under varied conditions, Toll-like receptor (TLR) 2/4 myeloid differentiation protein 88 deficiency neutrophil depletion. Measurements Main Results: localized within areas intraluminal small airways fibrosis tissue. Moreover, transcripts synthase enzymes significantly elevated versus both fluid increased Treatment low-molecular-weight abrogated murine a TLR2/4- 88–dependent fashion drove expansion alloantigen-specific T lymphocytes. Additionally, TLR-dependent signals stimulated neutrophilia that promoted rejection. In contrast, attenuated basal inflammation. Conclusions: These data suggest accumulation could by directly activating immune promote rejection neutrophilia.