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

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 muCi/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 X 10(3) of PAM in 88Sr-treated controls and 9.2 X 10(3) 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.

Radiation enhances silica translocation to the pulmonary interstitium and increases fibrosis in mice.

“…Various studies on the origin of the AM indicate that in normal animals, the population is maintained by local proliferation (3,4). This may occur in AM in situ (11 ) or in precursor cells in the interstitium (3,12), and several studies that indicate a local origin of AMs refer to pulmonary macrophage proliferation without distinguishing cellular location (13,14). In the present study, there was no reduction in AM in mice receiving radiation only, further supporting a local origin for these cells in monocyte-depleted animals.…”

GATA2 regulates dendritic cell differentiation

“…A reported selfrenewal capacity allows macrophages to survive for long periods. [45][46][47] Therefore, residing macrophages in the spleen may have selfrenewed to maintain the number of macrophages. In the present study, we examined only the number of macrophages and not their functions.…”

Characterization and quantification of alveolar monocyte-like cells in human chronic inflammatory lung disease

“…Subpopulations of AMs were identified in the lungs of normal rats [23][24][25], guineapigs [26], rabbits [27], and humans [3,5,28,29]. Several experimental studies have suggested that resident AM populations in the normal lung are maintained by local division of cells and that the influx of peripheral monocytes is not needed to sustain the AM population [6,30,31]. In contrast, BOWDEN and ADAMSON [7] postulated that under normal circumstances the predominant mechanism of macrophage production is direct passage of monocytes across the interstitium to the alveoli, and that only a smaller proportion of cells appears to arise after division of resident interstitial cells with subsequent migration to the alveoli.…”