GRANULOCYTE MACROPHAGE COLONY-STIMULATING FACTOR-DEFICIENT MICE SHOW NO MAJOR PERTURBATION OF HEMATOPOIESIS BUT DEVELOP A CHARACTERISTIC PULMONARY PATHOLOGY/

Mice homozygous for a disrupted granulocyte/macrophage colony-stimulat ing factor (GM-CSF) gene develop normally and show no major perturbati on of hematopoiesis up to 12 weeks of age. While most GM-CSF-deficient mice are superficially healthy and fertile, all develop abnormal lung s. There is extensive peribronchovascular infiltration with lymphocyte s, predominantly B cells. Alveoli contain granular eosinophilic materi al and lamellar bodies, indicative of surfactant accumulation. There a re numerous large intraalveolar phagocytic macrophages. Some mice have subclinical lung infections involving bacterial or fungal organisms, occasionally with focal areas of acute purulent inflammation or lobar pneumonia. Some features of this pathology resemble the human disorder alveolar proteinosis. These observations indicate that GM-CSF is not essential for the maintenance of normal levels of the major types of m ature hematopoietic cells and their precursors in blood, marrow, and s pleen. However, they implicate GM-CSF as essential for normal pulmonar y physiology and resistance to local infection.