Bone marrow-derived cells are required for the induction of a pulmonary inflammatory response mediated by CD40 ligation

The expression of inflammatory mediators by various cells following in vitr o CD40 ligation is well known. However, knowledge of the role and interacti on with these cells in the establishment and maintenance of in vivo immune- mediated inflammation Is limited. In this report, a chimeric mouse model ba sed on CD40 knockout and wild-type mice was used to assess the role of bone marrow (BM)-derived and non-BM-derived cells in a CD40-mediated pulmonary inflammation response. CD40+ BM-derived cells were required for initial cel l recruitment, pulmonary edema, and weight loss associated with this respon se. The structural CD40+ non-BM-derived cells of the lung, such as fibrobla sts, epithelial cells, and endothelial cells, could not by themselves estab lish any level of pulmonary inflammation, However, both the CD40+ BM-derive d cells and the structural CD40+ non-BM-derived cells of the lung were requ ired to maximize the level of pulmonary inflammation. Both B cells and T ce lls played a contributing role in macrophage recruitment and pulmonary edem a but neither contributed to the inflammation-associated weight loss. These experiments indicate that CD40+ BM-derived cells were critical to the indu ction of pulmonary inflammation and that alveolar macrophages, B cells, and T cells contributed to selective aspects of the response.