The pulmonary alveolar proteinosis in granulocyte macrophage colony-stimulating factor/interleukins 3/5 beta c receptor-deficient mice is reversed by bone marrow transplantation

Mice mutant for granulocyte macrophage colony-stimulating factor (GM-CSF) or the common receptor component (beta c) for GM-CSF, interleukin (IL)-3, and IL-5 exhibit a lung disorder Similar to human pulmonary alveolar proteinosis, a rare disease with congenital, infantile, and adult forms. Bone marrow transplantation and hematopoietic reconstitution of beta c mutant mice with wild-type bone marrow reversed the established disease state in the lungs, defining this disease as hematopoietic in nature. It is likely that the disease involves alveolar macrophages, as donor myeloid cell engraftment into the lungs of mutant recipient mice correlated with reverting both the disease and an abnormal macrophage morphology seen in the lungs of affected animals. Recombination Activating Gene-2 mutant donor bone marrow, which lacks the potential to develop lymphocytes, reversed the pathology in the lungs to the same extent as whole bone marrow. These data establish that certain lung disorders, if of cell-autonomous hematopoietic origin, can be manipulated by bone marrow transplantation.