Origin, Kinetics, and characteristics of pulmonary macrophages in the normal steady state.

Abstract

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.

Cellular requirements for tumor-specific immunity elicited by heat shock proteins: tumor rejection antigen gp96 primes CD8+ T cells in vivo.

“…2 indicate that 25-50% of T cells recover by -45 days after antibody injection. A significant proportion of functionally active macrophages are also expected to repopulate by 45 days or less (11). The protocol shown in Fig.…”

Ceramide Regulates Lipopolysaccharide-Induced Phosphatidylinositol 3-Kinase and Akt Activity in Human Alveolar Macrophages

“…They are characterized by distinct surface markers (78) and by distinct and unique signaling pathways (49,79). Alveolar macrophages have been shown to survive for extended times after a foreign insult (80,81). Because the lung is often the first site of exposure to environmental stimuli, it is logical that alveolar macrophages have developed a unique method of prolonging and modulating inflammatory responses.…”

Enhancement of the antigen-presenting function of monocytes by cholesterol: possible relevance to inflammatory mechanisms in extrinsic allergic alveolitis and atherosclerosis

“…We have also reported that levels of Ht-A-DQ and HLA-DP are signiiicanlly increased on alveolar macrophages in EAA and sarcoidosis compared with controls [9]. Alveolar macrophages are mainly derived from blood monoeytes, which migrate to the lungs where they complete their ditferentiation to mature alveolar macrophages [10,11]; and there is evidence that the infiltration of monocytes is increased in the lungs of patients with EAA [12]. Cells of the mononuclear phagocyte lineage show considerable phenotypic diversity, suggesting the existence of a variety of differentiation programmes associated with the expression of different gene products [13].…”