THE EFFECT OF AEROSOLIZED RECOMBINANT HUMAN GRANULOCYTE MACROPHAGE COLONY-STIMULATING FACTOR ON LUNG LEUKOCYTES IN NONHUMAN-PRIMATES

The number and function of myeloid cells in the lungs are critical determinants of health and disease. To examine whether these cells can be modulated in vivo by a colony-stimulating factor (CSF), recombinant human granulocyte macrophage-CSF (GM-CSF) was given to cynomolgus monkeys by either continuous intravenous infusion (7,200 U/kg/day) for 2 wk or by aerosol exposure to 10(7) on 1 or 2 consecutive days. At intervals after the initiation of GM-CSF administration, animals underwent bronchoalveolar lavage (BAL) and had peripheral blood sampled to characterize changes in lung and circulating phagocytic cells. Compared with animals exposed to bovine serum albumin, there was an Increase in the total number of BAL cells retrieved. This increase was greatest in animals receiving aerosolized GM-CSF, and it was the result of more macrophages and neutrophils. Both lung macrophages and blood neutrophils from animals exposed to aerosolized GM-CSF exhibited an augmented respiratory burst in response to phorbol myristate acetate. Lung macrophages from GM-CSF-exposed animals exhibited increased capacity to bind and/or ingest opsonized and unopsonized Staphylococcus aureus. Despite functional activation of lung phagocytic cells, biochemical analyses of BAL fluid for markers of lung injury revealed an increase in only some parameters in the GM-CSF group. Intravenous administration of GM-CSF had the expected effect on augmenting the number of myeloid cells in the bloodstream. Aerosolized GM-CSF produced a transient effect on circulating myeloid cell number between 3 and 5 days after exposure. These studies demonstrated that exogenous GM-CSF is capable of increasing the number and function of phagocytic cells in the lungs in addition to the peripheral blood compartment, and they suggest an important role for this cytokine in lung biology.