Radiation-induced chimeric mice were used to study the origin of pulmonary alveolar macrophages. Unlike in other studies, these radiation chimeras were prepared by using a special fractionated irradiation regimen to minimize the killing of alveolar macrophage colony-forming cells, putative local stem cells. For this study CBA mice with or without T6 chromosome marker were used. Under this experimental condition, the majority of alveolar macrophages in mitosis are of host origin even after 45 weeks. These data suggest that alveolar macrophages are a self-renewing population under normal steady-state conditions.

In this study the proliferation kinetics of pulmonary alveolar macrophages (PAMs) are determined using [3H]thymidine labeling, flow cytofluorimetry, metaphase arrest, and the percentage of labeled mitoses. The demonstration of in situ PAM proliferation is demonstrated beyond doubt. Comparison of the turnover time, calculated from cell kinetic parameters, with the experimentally determined migration times shows that the contribution proliferating PAMs make to their own population size is significant. Indeed, a strong case may be made to show that some 70% of the PAM population is produced by intra-alveolar divisions of "free" PAMs.

Abstract. This study of pulmonary alveolar macrophages (PAMs) involves two techniques, one following the migration of a cohort of labelled PAMs from the lung and the other involves the use of a continuous labelling method with [3H]TdR. In both studies, strikingly similar, probably biphasic curves are obtained that can be interpreted as indicating the existence of two proliferating cell populations with turnover times of ˜10 days and ˜35 days. It is suggested that one of these compartments is an intra‐alveolar PAM population whilst the other probably represents a precursor population. It is also possible to interpret the data as indicating a single, and probably solely intra‐alveolar, PAM population with a very skewed distribution of cell cycle times.

This paper supports the hypothesis that some form of pulmonary alveolar macrophage (PAM) production occurs within the lung in the normal steady state. The study involved monitoring the change in number of labelled PAMs following two modes of irradiation-the first with the thorax being irradiated and the rest of the mouse shielded, the second with the thorax shielded and the body irradiated. Also measurements of monocyte and PAM numbers after a single bone marrow irradiation were carried out. Finally, the labelling indices of monocytes in both control and thorax irradiated mice were measured.Both the number of monocytes and PAMs, along with the labelling indices of monocytes and PAMs after irradiation, indicate the independence of PAMs from a monocyte precursor population, and also provide evidence for a pulmonary origin of PAMs.

The aim of this study was to investigate the validity of the ICRP procedure of using average tissue/organ dose in estimating carcinogenic risk. It has been suggested that highly non-uniform exposure ('hot spots') is much more carcinogenic than an equivalent dose delivered uniformly. In a series of experiments, mice were irradiated with X-rays either uniformly to the thorax or non-uniformly with 72 1-mm microbeams which irradiated approximately 20 per cent of the total lung volume. Two experiments involving uniform irradiation showed a peaked tumour incidence curve with a maximum at 5 Gy. The first 'microbeam' study also produced a pronounced peak in the dose response with a maximum tumour incidence at 1 Gy average lung dose or 5 Gy to the irradiated lung tissue. This implied the use of average tissue dose might underestimate the carcinogenic hazard of non-uniform exposure. Later, more extensive, microbeam experiments failed to replicate this finding. The results were nearly similar to those for uniform irradiation, with a slight increase in tumour incidence from 2.5-5.0 Gy average lung dose. These results imply that for these irradiation conditions the ICRP dose averaging procedure remains valid.