Exogenous CD40 ligand induces a pulmonary inflammation response

Expression of CD40 on cells involved in the inflammatory response has lead to speculation that CD40 ligation could play an important role in the establishment of the inflammatory response. Upon treatment of wild-type CD40 mice with soluble CD40L-CD8 (sCD40L) fusion protein a pulmonary inflammatory response was induced that was not observed in identically treated CD40 knockout mice. This inflammatory response involved polymorphonuclear leukocyte migration into the alveolar space and the accumulation of alveolar macrophages with up-regulated Ia expression. Treatment of wild-type or IFN-gamma knockout mice with sCD40L induced pulmonary responses that were similar except that fewer neutrophils and macrophages accumulated in the lungs of the IFN-gamma knockout mice. This suggested that IFN-gamma plays a role in sCD40L-induced accumulation of inflammatory cells in the lung. The induction of pulmonary inflammation by exogenous sCD40L supports evidence derived in vitro by others that CD40 ligation can result in inflammatory responses and that sCD40L is a potent inflammagen.