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-C SF) or the common receptor component (beta c) for GM-CSF, interleukin (IL)-3, and IL-5 exhibit a lung disorder Similar to human pulmonary al veolar proteinosis, a rare disease with congenital, infantile, and adu lt forms. Bone marrow transplantation and hematopoietic reconstitution of beta c mutant mice with wild-type bone marrow reversed the establi shed disease state in the lungs, defining this disease as hematopoieti c in nature. It is likely that the disease involves alveolar macrophag es, as donor myeloid cell engraftment into the lungs of mutant recipie nt mice correlated with reverting both the disease and an abnormal mac rophage morphology seen in the lungs of affected animals. Recombinatio n Activating Gene-2 mutant donor bone marrow, which lacks the potentia l to develop lymphocytes, reversed the pathology in the lungs to the s ame extent as whole bone marrow. These data establish that certain lun g disorders, if of cell-autonomous hematopoietic origin, can be manipu lated by bone marrow transplantation.