The experimental model proposed in this study is designed to resolve fundamental questions concerning the origin and kiretics of alveolar macrophages (AM). AM cytokinetic and functional behavior will be studied in a monocytopenic and parabiotic mouse models. Monocytopenia will be induced by intravenous (iv) injection of 89Sr a bone seeking nuclide which selectively suppresses cell proliferation in bone marrow. It has been hypothesized that blood monocytes are the direct lineal antecedents of AM and that physiological renewal of AM depends exclusively on the sustained influx of monocytes. It is clear that by reducing levels of circulating monocytes a new approach can be made to study independent AM population dynamics. Tritiated thymidine (3HTdR) incorporation will serve as an index of AM proliferation. Alterations in AM pool size and kinetics, in the absence and presence of monocytes, will also monitor effects of monocyte depletion. Results from studies in 89Sr, treated hosts will be compared to cytokinetic data obtained from the unilateral 3HTdR labeling of parabiotically fused mice, a model which closely approximates the normal """"""""steady state"""""""" without having the disadvantage of using irradiated hosts. The working hypothesis of this study is that AM can proliferate independently, in the absence of monocyte influx. If incorrect, in the absence of antecedent monocytes the AM pool size will decline with a predictable slope; alternatively, if AM are in some part self-renewing, pool size should stabilize. Further, if incorrect labeled AM should be detectable in the lungs of recipient parabiont the donor of which is unilaterally labeled with 3HTdR; alternatively, even in the presence of labeled donor monocytes no labeled AM will be found in the recepient. Preliminary data using 89Sr treated mice support the hypothesis that AM are self-renewing.
