MECHANISMS OF IPS AFTER ALLOGENEIC BMT

University Of Michigan At Ann Arbor, Ann Arbor MI

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Abstract

Almost half of the pneumonias after allogeneic bone marrow transplant (BMT) are non infectious in origin, and are referred to as idiopathic pneumonia syndrome (IPS). During the first cycle of funding of this grant the authors have used well defined mouse models to investigate IPS pathophysiology after allogeneic BMT. Significant progress has been made in identifying two interrelated pathways of lung injury: (1) host antigen-non-specific inflammatory effectors, including endotoxin (LPS) and TNF which are linked through a gut-liver-lung axis; and (2) host antigen specific T cell effectors which home to the pulmonary interstitium and cause pneumonitis. In this first competing renewal of the grant, the investigators propose to investigate further the mechanisms of IPS lung injury using these well defined allogeneic BMT mouse models and to explore novel approaches to the prevention of such injury. The Specific Aims are: 1) to analyze the contribution of inflammatory effectors to IPS lung injury after allogeneic BMT, 2) to analyze the contribution of T cell effectors to IPS by injury after allogeneic BMT, and 3) to analyze the mechanisms of chronic lung injury after allogeneic BMT.