The Significance of Local Resident Pulmonary Alveolar Macrophage Proliferation to Population Renewal

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Abstract
The local proliferative capacity of resident pulmonary alveolar macrophages (PAM) was determined in normal CD-1 (ICR) mice and mice made severely monocytopenic with strontium-89 (89Sr). Intravenous injection of 2 μCi/gm BW 89Sr rendered mice monocytopenic for a 1-month period. During this time, in addition to there being no change in the size of the PAM population, flash 3HTdR labeling studies showed that at any one instant about 8.8 × 103 of PAM in 88Sr-treated controls and 9.2 × 103 PAM in 89Sr-treated mice were in S phase of the cell cycle. Metaphase arrest experiments using vincristine showed that in 88Sr-treated mice PAM entered M phase at a rate (rM) of 0.51%/hr with a duration of M (Tm) of 0.37 hr, whereas rM = 0.23%/hr with Tm = 0.14 hr for PAM in 89Sr-treated mice. These data suggest PAM population half-times of 131 hr in the presence of monocytes and 301 hr in the absence of monocytes. The data show that PAM proliferate locally; moreover, for intervals longer than the estimated half-time, PAM population size was unchanged. By following the accumulation of pulse 3HTdR-labeled mitotic figures it was found that in both 88Sr- and 89Sr-treated mice G2 = 3 hr and Ts = 11 hr. From these data a model of PAM population growth was used to show that PAM renewal may be accounted for by local proliferation alone. Taken together the data show that resident PAM populations may be sustained by local division of cells and that the influx of peripheral blood monocytes was not needed to sustain PAM.