Lungs cellular components

Fibers that persist within the lung or the mesothelium are capable of producing fibrogenic and tumorigenic effects in these tissues. Although the precise mechanisms by which asbestos fibers cause toxic injury have not been determined, data are available that indicate that both direct interaction between fibers and cellular components and cell-mediated pathways may be involved. In addition, the physical-chemical nature of the fiber appears to be an important determinant of toxicity. Though the various mechanisms are likely to interact extensively, they will be discussed individually below. 

Oxidation of cellular components by reactive oxygen species (ROS) and free radicals is involved in a variety of serious acute and chronic diseases inflammation [56], ischemia-reperfusion damage [57,58], lung disease [59], kidney damage [60], atherosclerosis, diabetes, allergies, cancer and aging [61]. 

Toxicokinetics describes the biokinetics of toxic substances. It includes the kinetic processes for toxic substances which govern the movement into, within, and from the bodies of human populations. The overall lead toxicoki-netic process includes (1) the uptake, i.e., absorption rate, of lead into the bloodstream from various body compartments such as the lung or G1 tract (2) movement within the bloodstream followed by transport internally to target tissues and their cellular components (3) retention within one or more tissues and finally (4) excretion from the body by various systemic pathways. Older literature made incorrect reference to lead toxicokinetics as lead metabolism, but the latter term is more correctly employed with toxic substances undergoing actual chemical transformation within such processes as addition or removal of chemical groups and oxidative or reductive changes. 

Figure 11.1 Ultrastructure of the human lung alveolar barrier. The tissue specimen is obtained via lung resection surgery. (A) Section through a septal wall of an alveolus. The wall is lined by a thin cellular layer formed by alveolar epithelial type I cells (ATI). Connective tissues (ct) separate ATI cells from the capillary endothelium (en) within which an erythrocyte (er) and granulocyte (gc) can be seen. The minimal distance between the alveolar airspace (ai) and erythrocyte is about 800-900 nm. The endothelial nucleus is denoted as n. (B) Details of the lung alveolar epithelial and endothelial barriers. Numerous caveolae (arrows) are seen in the apical and basal plasma membranes of an ATI cell as well as endothelial cell (en) membranes. Caveolae may partake transport of some solutes (e.g., albumin). (C) ATII cells (ATII) are often localised in the comers of alveoli where septal walls branch off. (D) ATII cells are characterised by numerous multilamellar bodies (mlb) which contain components of surfactant. A mitochondrion is denoted as mi.

The uptake of ozone relates directly to its reactions with substrates present in the lung lining fluid, a mechanism referred to by Postlewaite as reactive absorption [3]. The uptake of ozone is thus related not only to its concentration but also availability of substrates within the RTLF [4]. As these are numerous, ozone does not actually transit RTLF and hence cannot interact directly with the pulmonary epithelium. Rather it is consumed during reactions with compounds in this compartment (Fig. 2). Therefore, cellular responses to ozone are not a result of the direct reaction of ozone with cell surface component/receptors but rather are mediated through a cascade of secondary, free radical derived, ozonation products [2,4]. 

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