Peripheral Lung

Marcel Dbkker, Inc. 270 Madison Avenue, New York, New York 10016 

Long-Term Particle Clearance Pathways and Their Underlying Mechanisms 

Several clearanee pathways were recognized to play a potential role in the elimination of slowly dissolving, nonviable particles from the epithelium of the peripheral lungs  

Extracellular particle dissolution in the epithelial lining fluid 

Intracellular particle dissolution by alveolar macrophages (AM) and other phagocytic cells 

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Mace K, Bowman ED, Vautravers P, Shields PG, Harris CC, Pfeifer AM (1998) Characterisation of xenobiotic-metabolising enzyme expression in human bronchial mucosa and peripheral lung tissues. Eur J Cancer 34(6) 914—920. 

Table 11.3 Summary of the Expression Pattern and Activities of Phase I and Phase II Metabolic Enzymes and Various Peptidases/Proteases in Human Peripheral Lung Tissues, Primary Rat AEC Culture and Human Alveolar Epithelial Cell Line, A549.

Because the respiratory tract is an initial target of any air pollutant challenge, it usually receives primary attention in tests to determine irritant effects of exposure. Other aspects of interest include hematology, blood enzyme biochemistry, eye irritation, and p chomotor performance. Constriction of the large airways, maldistribution of ventilation due to narrowing in some small airways, constriction of peripheral lung units, and mechanical or gas diffusion impairment due to edema are possible effects of insult by pollutants. A variety of pulmonary tests is required to examine the possibilities. 

Antitrypsin (sheep) 52 kDa Aerosol (nebulized) Solution 50 % in 50 h lost from peripheral lung bioavailability. 16 % via lymphatics... 

Jin X, Shepherd RK, Duling BR, Linden J (1997) Inosine binds to adenosine receptors and stimulates mast cell degranulation. J Clin Invest 100(11) 2849-2857 Joad JP (1990) Characterization of the human peripheral lung adenosine receptor. Am J Respir Cell Mol Biol 2(2) 193-198... 

For humans, the overall chromium(VI)-reducing/sequestering capacities were estimated to be 0.7-2.1 mg/day for saliva, 8.3-12.5 mg/day for gastric juice, 11-24 mg for intestinal bacteria eliminated daily with feces, 3,300 mg/hour for liver, 234 mg/hour for males and 187 mg/hour for females for whole blood, 128 mg/hour for males and 93 mg/hour for females for red blood cells, 0.1-1.8 mg/hour for ELF, 136 mg/hour for pulmonary alveolar macrophages, and 260 mg/hour for peripheral lung parenchyma. Although these ex vivo data provide important information in the conversion of chromium(VI) to reduced states, the values may over or under estimate the in vivo reducing capabilities (De Flora et al. 1997). 

The AERx, developed by Aradigm (Hayward, CA), is a metered dose liquid inhaler designed to deliver various pharmaceutical compounds to the peripheral lungs. The system, as shown in Fig. 10, consists of a unit dose disposable container equipped with a nozzle array, a piston assembly, and electronics associated with breath actuation and compliance monitoring functions. ... 

Peripheral lung infiltrates with blood eosinophUia are rare effects of sulfasalazine. SuUasalazine-induced hjrper-sensitivity lung disease with simultaneous Legionella pneumophila infection has been reported for the first time (35). 

DC infiltrates, albeit of smaller numbers, have also been observed in BAL fluids from rodents in a model of subacute peripheral lung inflammation (Havenith et al., 1992), and in chronic inflammation in human smokers (Soler et al., 1989). 

The initial indication that the fiinction(s) of lung IXls may be regulated by local Macs came from our initial studies on the isolation of peripheral lung DCs from the rat. These experiments identified the most potent APC population in coUagenase digest of parenchymal lung tissue as DCs, but further demonstrated that expression of their fidl APC potential required initial elimination of contaminating Macs (Holt et al., 1985). Similar results were obtained with airway epithelial DCs (Holt et al., 1988). 

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