Effects of macrophage-CSF on pulmonary-macrophage repopulation after bone marrow transplantation

Pulmonary infections are important causes of morbidity and mortality in imm unosuppressed patients after transplantation. After experimental irradiatio n and syngeneic bone marrow transplantation in mice, macrophages show reduc ed repopulation in the lung compared with that in other tissues. Macrophage s are major microbicidal immune effector cells in host pulmonary defense. T herefore, we examined the role of locally applied cytokines for macrophage repopulation in the lung. An accelerated repopulation of macrophages in the lung was observed after intranasal application of macrophage-colony stimul ating factor (M-CSF), but this effect was not enhanced by a combination of M-CSF with interleukin (IL)-3, Local proliferation contributed to this effe ct. Macrophages in the lung tissue of M-CSF-treated mice displayed greater secretion of IL-6, whereas M-CSF treatment did not enhance the gene express ion of other macrophage-specific chemokines. The role of M-CSF treatment wa s determined in pulmonary murine cytomegalovirus infection using an irradia tion/reconstitution model. The M-CSF treatment had no effect on virus load in the lung tissue. However, phosphate-buffered saline-treated mice seemed to develop stronger inflammation after viral infection than M-CSF-treated m ice. We conclude that local M-CSF treatment modulates cellular inflammation in the lung during immunosuppression.