Pulmonary macrophages of mice in the steady state were isolated by lavage with PBS containing EDTA and subsequent enzymatic digestion of tissue with pronase and DNA-ase. By this method, the total pulmonary macrophage population was obtained in two cell suspensions, one with a pure population of pulmonary alveolar macrophages (PAM) and the other with a mixed population of pulmonary alveolar and pulmonary tissue macrophages (PTM). The morphological, cytochemical, and functional characteristics of both PAM and PTM were like those of mature tissue macrophages except for the presence of C3 receptors. These receptors were almost absent on PAM and present on a larger number of cells in the mixed population of PAM and PTM. The total pulmonary macrophage population of mice in the steady state is approximately equal to 2 x 10(6), of which about 93% are PAM and about 7% are PTM. In labeling experiments with 3H-thymidine, the low in vitro labeling indices (less than 3%) for both PAM and the mixture of PAM and PTM, showed that both are essentially nondividing cells. In vivo labeling studies showed an increase in the number of labeled macrophages that can only be attributed to labeled monocytes migrating into the lungs. Additional evidence was provided by a decrease in the labeling indices of pulmonary macrophages when mice were treated with hydrocortisone acetate, which causes a severe monocytopenia, thus preventing monocyte influx into the lungs. Confirmation of the bone marrow origin was obtained in mice labeled after x-irradiation with partial bone marrow shielding: labeled pulmonary macrophages were found in the exposed lungs. In all experiments, the labeling indices were identical in the two macrophage populations isolated. These results show that the influx of monocytes is the source of cell renewal for the pulmonary macrophages. No indications for an interstitial division or maturation compartment in the lung were found. Quantitation of the efflux of labeled monocytes from the blood, and the number of labeled pulmonary macrophages, showed that in the steady state about 15% of the monocytes leaving the circulation become pulmonary macrophages and that the turnover time of pulmonary macrophages is approximately equal to 27 d.

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The main defenders of the respiratory organs against microorganisms and other foreign substances are the pulmonary macrophages. The majority of these cells, which belong to the mononuclear phagocyte system (1), are normally located in the alveolar spaces, where they phagocytize surfactants (2) and various substances introduced via the airways ; the remainder occur in the interstitial lung tissue (3) . The origin and kinetics of the pulmonary macrophages have been controversial, mostly because of differences in the interpretation of DNA-labeling characteristics in the absence of accurate quantitative information. Recently, a method developed to study the total pulmonary macrophage population by optimal lavage of the airways followed by enzyme digestion of lavaged lung tissue after removal of circulating monocytes from the pulmonary blood vessels enabled us to demonstrate that the great majority of the pulmonary macrophages of mice in the normal steady state derive from circulating monocytes originating in the bone marrow (4), and that local proliferation of mononuclear phagocytes does not play a significant role in the maintenance of the pulmonary macrophage population . ' The origin and kinetics of the increased number of pulmonary macrophages during acute inflammatory reactions are, however, still a matter of debate . On the basis of studies done of inflammation induced by various stimuli ranging from inert particles to pathogenic microorganisms and noxious gases in various animal models, both an influx of circulating monocytes and interstitial multiplication of macrophages or macrophage-precursor cells have been claimed to contribute to the pulmonary macrophage population under these conditions (5-9) .The present report concerns the macrophage kinetics during an inflammatory reaction in the lungs after the intravenous injection of heat-killed bacillus CalmetteGuerin (BCG).2 The kinetic patterns were studied by following the course and determining the DNA-labeling characteristics of both the circulating monocytes and the total macrophage population, i.e., the alveolar and interstitial macrophages. 2 Abbreviatons used in this paper. AML, alveolar-macrophage-like ; BCC, bacillus Calmette-Guerin ; C, complement ; HC, hydrocortisone acetate; NAML, non-alveolar-macrophage-like ; t DNA-synthesis time; ZN, Ziehl-Neelsen . J . Exp . MED .

Azithromycin, a recently introduced antibiotic, offers the potential advantages of short-course administration and lower toxicity compared to other macrolides. Approved for the treatment of mild pneumonia, this drug was investigated in a study of patients hospitalized for community-acquired pneumonia. In an open-labelled randomized study, oral azithromycin was compared with intravenous benzylpenicillin in patients suspected to have pneumococcal pneumonia. Azithromycin was also compared with erythromycin, both administered orally, in all other patients. Three hundred thirty-four patients with community-acquired pneumonia were hospitalized, 108 of whom were randomized; 104 could be evaluated. A need for intravenous therapy was the most common reason for exclusion. In the pneumococcal group, 35 patients received azithromycin and 29 benzylpenicillin. The clinical and radiological success rate achieved with azithromycin (83%) was considerably higher than that achieved with benzylpenicillin (66%), though the difference was not significant. In the non-pneumococcal group, 19 patients received azithromycin and 21 erythromycin; no differences in the success rate were found (79% and 76%, respectively). Eight patients on azithromycin had a blood culture positive for Streptococcus pneumoniae; in three of these patients therapy was changed. None of the five patients with pneumococcal bacteraemia who received benzylpenicillin required a change in therapy. It is concluded that oral azithromycin, administered as short-course therapy, is an appropriate antibiotic for treating patients with community-acquired pneumonia. However, it is not yet certain that azithromycin is a good choice for patients with pneumococcal bacteraemia.

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