Local Production of Proteins in Normal Human Bronchial Secretion

Abstract

Concentrations of albumin, IgG, IgA, IgM, α₁-acid glycoprotein, α₁-anti-trypsin, α₂-macroglobulin, transferrin, haptoglobin, and coeruloplasmin were determined by radial immunodiffusion in the blood sera and bronchial washings of 8 patients without clinical, radiologic or bronchoscopic evidence of lung diseases. The local production of the proteins was calculated with a formula used by Deuschl and Johansson for the estimation of local synthesis of bronchial immunoglobulins. The formula was completed by a reduction factor established by the authors, based on their previous investigations The calculations indicated that the individual proteins were secreted locally in various percentages of the total amount found in the secretion, as follows: IgG, 37%; IgA, 84.5%; transferrin, 44.5%, α₁-antitrypsin, 15.2%; coeruloplasmin, 11.3%. Local synthesis of IgM was found only in 3 patients. The α₁-acid glycoprotein and the haptoglobin do not seem to be secreted locally by the normal bronchial mucosa; they reach the mucus from blood only, through ultrafiltration

ToF-SIMS mediated analysis of human lung tissue reveals increased iron deposition in COPD (GOLD IV) patients

“…ToF-SIMS does not discriminate between oxidized, ferric (Fe 3+ ) iron and soluble ferrous (Fe 2+ ) iron. At physiological pH, iron pre-dominantly exists as insoluble ferric iron, bound to carrier proteins such as transferrin 51 , ferritin 9 , lactoferrin 52 , ceruloplasmin 53 and/or lipocalin 2 8 , or unbound in the form of cell free hemoglobin/heme or non-transferrin bound iron (citrate or acetate bound iron), all of which are found in the BALF. To be absorbed, iron must be in the ferrous (Fe 2+ ) state.…”

Iron Homeostasis in the Lungs—A Balance between Health and Disease

“…The epithelial surface of the respiratory tract is covered by a thin layer of fluid containing high levels of antioxidant molecules, such as ascorbic acid, reduced glutathione, and mucin [14]. Furthermore, human airway secretions contain transferrin and lactoferrin, and glycoproteins are able to bind iron and maintain a chemically inert form [15,16]. Iron bound to transferrin or lactoferrin can be taken up by epithelial cells through their receptors, namely transferrin receptor 1 (TfR1) and lactoferrin receptor (LfR), respectively, to be stored safely bound to ferritin (Figure 2), a multimeric iron storage protein consisting of 24 subunits of heavy and light chains capable of accommodating up to 4000 iron atoms [17,18,19].…”

“…Iron export via FPN is combined with iron oxidation from Fe 2+ to Fe 3+ , mediated by ceruloplasmin (or hephaestin in the basal membrane of duodenal enterocytes) (Figure 1) [83,84]. Interestingly, ceruloplasmin was detected in human bronchial lavage fluid, suggesting that it might be involved in FPN-mediated iron export in the lung [15]. Note that the pH of lung fluids (e.g., the alveolar lining fluid) may affect the complex process of spontaneous oxidation of ferrous to ferric iron following a sigmoid shaped oxidation rate in relation to pH [85].…”

Human bronchoalveolar lavage fluid: Two-dimensional gel electrophoresis, amino acid microsequencing and identification of major proteins

“…These proteins could well occur in BAL fluid as a result of a passive diffusion across the bronchoalveolar/blood barrier, reflecting its permeability [20]. However, although the liver is the primary site of synthesis of many of these proteins (except immunoglobulins, complement factors, and hemoglobin), several publications have shown a local intrapulmonary production of most of these proteins, including fibrinogen g-A chain [21], a 1 -antitrypsin [22], transferrin [23], complement C3 [24], complement C4 [25], apolipoprotein A-1 [26], immunoglobulins [27], and b 2 -microglobulin [28]. This last protein was identified as one spot (B200) by N-terminal sequencing, although the b 2 -microglobulin corresponds to two spots in the SWISS-2D PAGE amniotic fluid map [29].…”