Substantial progress has been made in understanding the rate, the pathways, and the mechanisms regulating alveolar protein removal from the uninjured lung. Whole animal studies and cellular studies have demonstrated that the majority of alveolar epithelial protein clearance occurs by passive nondegradative diffusional pathways. Some evidence, however, has been recently presented that alveolar epithelial cells express an albumin-binding receptor as well as a polymeric immunoglobulin receptor, both of which might be important for alveolar epithelial clearance of protein. However, the contribution of these receptors requires further studies. Little is known about alveolar clearance of protein during pathological conditions; further studies are required to determine the roles of the different cell types in the lung for removal of protein from the alveolar spaces of the lung. Alveolar macrophages are likely to play an important role in the degradation and removal of insoluble protein from the distal air spaces after acute lung injury. In conclusion, the present data suggest that most proteins and peptides deposited on the epithelial surfaces in the distal air spaces are cleared as intact molecules, predominantly via paracellular routes. The contribution of pinocytic processes appear to be of minor importance for translocation of bulk quantities of proteins or peptides across the alveolar epithelium.
The passage of different-sized marker molecules over the lower respiratory tract into the blood circulation during pulmonary inflammation induced by dextran, endotoxin [i.e., lipopolysaccharide from Escherichia coli (LPS)], or ferritin was assessed in the rat. Bovine immunoglobulin G (BIgG, mol wt = 150,000 Da), bovine serum albumin (BSA, mol wt = 67,000 Da), and the nonapeptide 1-deaminocysteine-8-D-arginine vasopressin (dDAVP, mol wt = 1,067 Da) were used as permeability markers after intratracheal instillation. The pathophysiological indexes of a proceeding lung inflammation were increased total cell number, changed leukocyte proportions and increased total protein content obtained in bronchoalveolar lavage, and lung edema formation shown as an increased lung wet-dry weight difference. Intratracheal instillation of dextran induced a moderate neutrophil invasion into the lungs but had no effect on the passage of the different markers over the lungs (BIgG 1.8 +/- 0.6%, BSA 3.5 +/- 1.2%, dDAVP 26.1 +/- 20.7%) compared with control rats instilled with the markers alone (1.8 +/- 0.4%, 4.1 +/- 1.3%, 20.0 +/- 3.8%, respectively). Endotoxin administration resulted in markedly higher lavage cell counts and lung edema concomitantly with an increased lung passage of the markers (3.2 +/- 0.9%, 22.0 +/- 6.1%, 33.3 +/- 12.0%, respectively; P less than 0.01-P less than 0.001). The highest marker passage was obtained when the inflammation was most severe, i.e., after ferritin administration (17.6 +/- 2.3%, 60.0 +/- 6.7%, 41.6 +/- 6.9%, respectively; P less than 0.001), which resulted in markedly elevated lavage cell numbers and protein content as well as edema formation.(ABSTRACT TRUNCATED AT 250 WORDS)
The role of cortisol in the prenatal development of digestive enzymes in the abomasum (prochymosin and pepsinogen) and pancreas (amylase, trypsin, chymotrypsin) has been investigated in the fetal lamb during late gestation. The abomasum and pancreas were collected from 22 unoperated control fetuses (99-145 days gestation; term, 145 +/- 2 days), from seven pairs of twins infused with either saline or cortisol for five days preceding delivery at 127-133 days, and from four 139-143-day-old fetuses adrenalectomized at 120-123 days. Developmental increases (2-8-fold) occurred in protease concentrations in the fetal abomasum and in amylase and chymotrypsin contents in the fetal pancreas. These increases paralleled the normal prepartum rise in fetal plasma cortisol. In addition, the enzyme values were significantly higher in cortisol-infused than in saline-infused fetuses (with the exception of pancreatic amylase) and were significantly lower in adrenalectomized fetuses than in control fetuses at term. The pH of abomasal fluid remained neutral (pH 6.8-8.0) during late gestation and was not affected by cortisol treatment or adrenalectomy. The results suggest that cortisol stimulates the development of the exocrine abomasum and pancreas in fetal sheep and may, thereby, increase the digestive capacity in neonatal lambs. Compared with the pig, another long-gestation species, the sheep has an early development of gastric pepsinogen but a late development of gastric acidity and pancreatic protease activities.
Urinary recovery of intratracheally instilled polyethylene glycol polymers (PEG:s) in the molecular weight range 722-1294 Da (PEG 1000) was studied under normal conditions and during experimentally induced lung damage in rats. The urinary PEG recoveries were between 30-60% under normal conditions, with a selectivity for smaller PEG:s. No significant differences in the urinary PEG molecular weight profiles were found between 30 days old and adult rats; i.e. they had similar PEG 1162/810 (molecular weights) urinary recovery ratios (0.78 +/- 0.25 and 0.69 +/- 0.27, respectively, p > 0.05). In rats instilled with PEG 1000 and ferritin (5 mg.kg-1 body weight), the urinary recovery was increased for PEG:s with molecular weights greater than 1030 Da; i.e. a higher PEG 1162/810 recovery ratio (1.44 +/- 0.58, p < 0.01) was obtained. Rats instilled with PEG 1000 and crocidolite asbestos fibres (5 mg.kg-1 body weight) showed higher urinary recoveries for PEG:s greater than 854 Da, resulting in a higher PEG 1162/810 ratio (1.47 +/- 0.59, p < 0.01). By adding the iron-chelator, desferrioxamine, to the crocidolite-instillate, the urinary recoveries and the PEG 1162/810 ratio (0.97 +/- 0.47) were reduced, indicating a restored molecular weight selectivity of the lung. Thus, in rats, PEG 1000 passes via the respiratory tract in large amounts which is dependent on the molecular weight. This passage was increased after ferritin- or crocidolite instillation, indicating that the barrier function of the respiratory tract was impaired due to local tissue damage, and that iron may play an important role in this.
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