© 2003 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume IIA: Biocompatibility, Landes Bioscience, Georgetown, TX, 2003

15.4.3.2.2 Phagocytosis in Lung Vasculature

Besides geometrical filtration in the lung vasculature (Section 15.4.2.1), in some mammals, such as (but not exclusively) ruminants, particles may also be removed from blood passing through the pulmonary vasculature by active pulmonary intravascular mononuclear phagocytes (PIMPs) or macrophages (PIMs) residing in the pulmonary capillaries [2912-2919]. PIMs are large (20- to 80-micron diameter) mature macrophages bound to the pulmonary capillary endothelium. These cells have an irregular shape, an indented nucleus, lysosomal granules, pseudopods, phagosomes and phagolysosomes, tubular micropinocytosis vermiformis structures, and a fuzzy glycocalyx [2913, 2920]. PIMs attach preferentially to the thick portion of the air-blood barrier [2913, 2921], thus minimizing potential interference with gas exchange at the air-blood barrier [2919]. Histologic experiments on the rat found that the lung microvasculature contained ~1 mononuclear phagocyte (half of them active) per alveolus and ~0.3 active neutrophils per alveolus [2922]. About 15 m² of the sheep lung capillary endothelial surface is covered with PIMs [2920].

In 13 nonhuman animal species, 20-nm gold particles clearance half-lives ranged from 1-2 minutes, with 90% clearance after 10 minutes in all species [2919]. 0.5-micron iron oxide particles were cleared during the first lung pass in sheep and calves [2919]. In sheep injected IV with 1-micron latex microbeads, 70% of the beads were caught in the phagosomes of pulmonary intravascular macrophages after 1 hour [3317]. Warner et al [2923] showed >90% uptake of IV injected P. aeruginosa bacteria in sheep lungs.

Do humans have PIMs? Dehring and Wismar [2924] reported large mononuclear cells with phagocytic vacuoles in clinical human lung biopsy specimens. But a morphometric study of human lung [2925] showed no macrophages or macrophage-like cells in the pulmonary capillaries and particle uptake studies suggest that humans do not normally have resident PIMs [2919]. (Humans do have pulmonary alveolar macrophages; Section 15.4.3.3.3.) In humans, IV-injected radiolabeled colloid is usually taken up by hepatic (Section 15.4.3.2.3) and splenic (Section 15.4.3.2.4) macrophages – the basis of liver-spleen scans used clinically [2926] – and detectable lung uptake has occasionally been seen, usually in cases of severe liver damage [2926]. It may be that pulmonary uptake in humans is enhanced when Kupffer cells are compromised [2927], or when organ injury results in monocyte margination in lung capillaries and in the subsequent differentiation of these monocytes into mature macrophages [2928, 2929].

Last updated on 30 April 2004