Localization of Macrophages in the Human Lung via Design-Based Stereology.

RATIONALE: Interstitial macrophages (IMs) and airspace macrophages (AMs) play critical roles in lung homeostasis and host-defense and are central to the pathogenesis of a number of lung diseases. However, the absolute numbers of macrophages and the precise anatomic locations they occupy in the healthy human lung have not been quantified. OBJECTIVES: To determine the precise number and anatomic location of human pulmonary macrophages in non-diseased lungs and to quantify how this is altered in chronic cigarette smokers. METHODS: Whole right upper lobes from 12 human donors without pulmonary disease (6 smokers and 6 nonsmokers) were evaluated using design-based stereology. CD206+/CD43+ AMs and CD206+/CD43- IMs were counted in five distinct anatomical locations using the optical disector probe. MEASUREMENTS AND MAIN RESULTS: An average of 2.1x10(9) IMs and 1.4x10(9) AMs were estimated per right upper lobe. 95% of AMs were contained in diffusing airspaces and 5% in airways. 78% of IMs were located within the alveolar septa, 14% around small vessels and 7% around the airways. The local density of IMs was greater in the alveolar septa than in the connective tissue surrounding the airways or vessels. The total number and density of IMs was 36-56% greater in the lungs of cigarette smokers versus nonsmokers. CONCLUSIONS: The precise locations occupied by pulmonary macrophages were defined in non-diseased human lungs from smokers and nonsmokers. IM density was greatest in the alveolar septa. Lungs from chronic smokers had increased IM numbers and overall density, supporting a role for IMs in smoking-related disease.