AN ALTERED LECTIN BINDING TO MUCUS GLYCOPROTEIN IN GOBLET CELLS OF HUMAN TRACHEOBRONCHIAL EPITHELIUM AMONG FORMER MUSTARD-GAS WORKERS

Lectins, which are well known to have an ability to bind with specific carbohydrate residues of glycoprotein, have been used to examine cellular changes associated with malignant transformation. For the analysis of mucus glycoprotein of goblet cells in the tracheobronchial epithelium, 192 paraffin-embedded sections from 54 autopsy cases including the cases with a history of mustard-gas (MG) exposure were stained with seven plant lectins using PAP method. PNA binding with no neuraminidase treatment as well as BSA-1 binding was observed most frequently in MG-exposed lung cancer cases. The proportion of cases positive for SBA binding in MG-exposed and/or lung cancer cases had a statistical difference from non-MG-exposed non-lung cancer cases. These observations may indicate a large heterogeneity in oligosaccharide chains of mucus glycoprotein and suggest its incomplete or abnormal synthesis, which is most likely to be due to previous exposure to carcinogen, such as MG. ACTA PATHOL. JPN. 37:537–548, 1987.     

Early cancer and related lesions in the bronchial epithelium in former workers of mustard gas factory

The bronchial epithelium in stepwise transverse sections was examined histologically in 66 male autopsy cases, composed of the groups of 19 mustard gas (MG) ex-workers with lung cancer, 17 MG ex-workers with non-lung cancer, 10 non-MG lung cancer cases, and 20 non-MG non-lung cancer cases. Foci of moderate or severe atypical cellular lesion or dysplasia, or of carcinoma in situ (CIS) in total slides of each group, were counted as 146 in 3,485, 72 in 2,226, 70 in 3,797, and 18 in 4,611, respectively. The relative frequency of moderate or severe dysplasia and CIS in MG exposed non-lung cancer cases resembled that found in lung cancer cases of both MG and non-MG exposed. Seven CIS lesions were detected from among all MG-exposed cases and one CIS was found in a non-MG lung cancer case. Six out of eight CIS examples were adjoined by dysplasia. A multi-variate analysis revealed a significant correlation between the incidence of atypical lesions and MG exposure, though the incidence of atypical lesions was also influenced significantly by age, smoking, and chronic bronchitis. The incidence of atypical lesions was significantly higher in cases of squamous cell lung cancer than those of other histological types, particularly small cell cancer.     

EARLY CANCER AND RELATED LESIONS IN THE BRONCHIAL EPITHELIUM IN FORMER WORKERS OF MUSTARD GAS FACTORY

The bronchial epithelium in stepwise transverse sections was examined histologically in 66 male autopsy cases, composed of the groups of 19 mustard gas (MG) ex-workers with lung cancer, 17 MG ex-workers with non-lung cancer, 10 non-MG lung cancer cases, and 20 non-MG non-lung cancer cases. Foci of moderate or severe atypical cellular lesion or dysplasia, or of carcinoma in situ (CIS) in total slides of each group, were counted as 146 in 3,485, 72 in 2, 226, 70 in 3,797, and 18 in 4,611, respectively. The relative frequency of moderate or severe dysplasia and CIS in MG exposed non-lung cancer cases resembled that found in lung cancer cases of both MG and non-MG exposed. Seven CIS lesions were detected from among all MG-exposed cases and one CIS was found in a non-MG lung cancer case. Six out of eight CIS examples were adjoined by dysplasia. A multi-variate analysis revealed a significant correlation between the incidence of atypical lesions and MG exposure, though the incidence of atypical lesions was also influenced significantly by age, smoking, and chronic bronchitis. The incidence of atypical lesions was significantly higher in cases of squamous cell lung cancer than those of other histological types, particularly small cell cancer.     

Cholera enterotoxin-induced mucus secretion and increase in the mucus blanket of the rabbit ileum in vivo.

The in vivo rabbit ileum was used to study the relationship of cholera enterotoxin-induced water and electrolyte secretion and mucus secretion and to determine whether the enterotoxin influenced the intestinal mucus blanket. In experiments in which luminal fluid viscosity was used to assess mucus secretion, it was found that while cholera enterotoxin induced a sustained secretion of water and electrolytes, the toxin-induced mucus hypersecretion was short lived (3 to 5 h) and subsequent exposure of the mucosa to cholera enterotoxin or prostaglandin E1 did not stimulate mucus secretion further. Dibutyryl cyclic AMP and theophylline caused a modest mucus secretion in ileal loops which differed from that of cholera enterotoxin in both magnitude and in the fact that the mucus secretion occurred 2 to 3 h after the onset of water and electrolyte secretion. An oral replacement solution was used in the ileum to reduce the enterotoxin-induced loss of water and electrolytes into the lumen. While such a solution slowed the appearance of acidic glycoprotein in the intestinal lumen, it did not change the amount of glycoprotein secreted over a 7-h period, suggesting that toxin-induced mucus secretion was not simply due to a flushing action of the experimentally caused diarrhea. To assess mucus blanket thickness, neutral glycoprotein was recovered from the blanket of rabbit ileal loops 7 h after exposure to cholera enterotoxin and the thickness of the mucus blanket was measured directly 4 and 18 h after toxin exposure. Both methods indicated that even though cholera enterotoxin-induced mucus hypersecretion had subsided and there was histological evidence of goblet cell mucin depletion, there was a sustained increase in mucus blanket thickness that was detectable for at least 18 h after mucosal enterotoxin exposure.     

Pseudomonas aeruginosa outer membrane adhesins for human respiratory mucus glycoproteins.

The attachment of Pseudomonas aeruginosa to human respiratory mucus represents an important step in the development of lung infection, especially in cases of cystic fibrosis. For this purpose, microtiter plate adhesion assays have been developed and have suggested that nonpilus adhesins of P. aeruginosa are the most important ones for binding to human respiratory mucins. In order to characterize these mucin-binding adhesins, outer membrane proteins (OMP) from two adhesive strains, 1244-NP and PAK-NP, and their poorly adhesive rpoN mutants, 1244-N3 and PAK-N1, were prepared by a mild extraction with Zwittergent 3-14. Mucin-binding adhesins were detected after polyacrylamide gel electrophoresis and blotting of the OMP on nitrocellulose replicas, using human bronchial mucins labeled with 125I. The binding properties of these OMP with lactotransferrin, another glycoprotein abundant in respiratory mucus, were also studied. Radiolabeled mucins detected four bands at 48, 46, 28, and 25 kDa with strain PAK-NP. With the nonmucoid strain 1244-NP, five bands were observed at 48, 46, 42, 28, and 25 kDa. The bands at 48 and 25 kDa were also visualized by radiolabeled lactotransferrin. These bands were partially or completely displaced by nonradiolabeled respiratory mucin glycopeptides but not by tetramethylurea, suggesting that they recognized carbohydrate sites. In contrast, the poorly adhesive strains showed weakly binding bands. These results demonstrate that outer membranes from two different nonpiliated P. aeruginosa strains express multiple adhesins with an affinity for human respiratory mucins and/or lactotransferrin.     

Lectin binding patterns of alveolar epithelium and subepithelial seromucous glands of the bronchi in sepsis and controls – an approach to characterize the non-specific immunological response of the human lung to sepsis

A delayed or deficient immunological protection as well as an overstimulation of the mucosal immune system may act as possible additional promoters of sepsis-induced lung injury in patients suffering from a severe septic condition. Lectin-binding patterns in pulmonary tissue samples obtained at autopsy from septic patients and control individuals were studied using 11 carbohydrate-specific lectins (Con A, UEA, GSA I, GSA II, MPA, PNA, Jac, WGA, MAA, LPA, and SNA). There were no differences in the secretory product of serous parts of bronchial glands detectable in the two study groups, whereas lectin binding patterns of alveolar epithelium and mucous parts of subepithelial seromucous glands were different in sepsis cases when compared to controls. Apart from differences in binding sites for alpha-mannose, N-acetyl-neuraminic acid and alpha-(2-6)-galactose (as detected by different expression for Con A, MAA and SNA) in the two study groups, the main finding was that no binding sites for alpha-N-acetyl-galactosamine (as investigated by MPA immunoreactivity) could be detected on alveolar epithelial cells and mucous parts of subepithelial seromucous glands in sepsis cases in contrast to the presence of such binding sites in the control cases. We hypothesize that the finding of an altered secretory product of alveolar epithelial cells and bronchial glands in sepsis may be a result of specific carbohydrate deprivation or consumption, respectively, possibly due to direct bacterial effects or pathogenetic events in response to bacterial toxins during the complex cascade of the host's systemic inflammatory response in sepsis. The altered type of mucus glycoprotein physiologically secreted by alveolar epithelium and mucous parts of subepithelial seromucous glands of the bronchi with subsequent loss of a considerable proportion of protection of the mucosal barrier in sepsis may play an important additional role in the development of sepsis-induced lung injury.     

Pulmonary mucinous cystic tumors of borderline malignancy

Mucus-filled cystic tumors of low or borderline malignant potential, well recognized in ovary and appendix, have received little attention in the lung. We present data on 11 patients, all of whom had solitary pulmonary nodules resected in which mucus was the major histologic component. Prognosis appears good; no patient had developed local recurrence or metastatic spread of tumor (follow-up, 1 to 9.5 years; mean, 4.7 years). Columnar mucus-producing cells lined the cysts in all cases, with cytologic and architectural atypia varying from minimal to microscopic foci of carcinoma; paucicellular mucus dissection into surrounding lung analogous to pseudomyxoma peritonei was seen in seven cases. The histologic and clinical findings are consistent with a mucinous cystic tumor of low or borderline malignant potential.     

Lipopolysaccharide Induces Mucus Cell Metaplasia in Mouse Lung

A murine model of lipopolysaccharide (LPS)-induced airway inflammation and epithelial cell phenotypic change, and the time courses of these events are described. A single intratracheal instillation of Pseudomonas aeruginosa LPS in mice resulted in massive recruitment of neutrophils to the lung 2 d after treatment as assessed by differential cell counts of the inflammatory cells in bronchoalveolar lavage fluid and histologic assessment of hematoxylin and eosin (H&E)-stained lung sections. The LPS-induced neutrophilic inflammation subsided substantially on Day 4 and essentially vanished by Day 7. Airway epithelial mucus cells were not detected by Alcian blue periodic acid-Schiff staining until Day 4 after LPS treatment and became more abundant in number as well as in mucus content on Day 7. The expression of Muc5ac messenger RNA (mRNA) as well as glycoprotein was enhanced on Day 2, peaked on Day 4, and decreased on Day 7, whereas enhanced expression of mucin core 2 beta6 N-acetylglucosaminyltransferase (C2GnT)-M mRNA was not detected until Day 4 and peaked on Day 7. The expression of C2GnT-L mRNA in the lung, a marker for activated leukocytes as well as mucus cells, peaked on Day 2 and remained moderately high until Day 7. C2GnT-L mRNA expression in LPS-treated lung correlated with the presence of neutrophils and the appearance of mucus cells in the airway epithelium. We conclude that mucus cell metaplasia and hyperplasia can be generated in mouse lungs with a single intratracheal instillation of LPS. In addition, C2GnT-M may serve as a marker for mucus cells in mouse lung. This LPS-induced mucus cell metaplasia and hyperplasia model should be useful for the study of Pseudomonas-induced airway mucus hypersecretory diseases.     

The streptomycin-treated mouse intestine selects Escherichia coli envZ missense mutants that interact with dense and diverse intestinal microbiota

Previously, we reported that the streptomycin-treated mouse intestine selected nonmotile Escherichia coli MG1655 flhDC deletion mutants of E. coli MG1655 with improved colonizing ability that grow 15% faster in vitro in mouse cecal mucus and 15 to 30% faster on sugars present in mucus (M. P. Leatham et al., Infect. Immun. 73:8039-8049, 2005). Here, we report that the 10 to 20% remaining motile E. coli MG1655 are envZ missense mutants that are also better colonizers of the mouse intestine than E. coli MG1655. One of the flhDC mutants, E. coli MG1655 ΔflhD, and one of the envZ missense mutants, E. coli MG1655 mot-1, were studied further. E. coli MG1655 mot-1 is more resistant to bile salts and colicin V than E. coli MG1655 ΔflhD and grows ca. 15% slower in vitro in mouse cecal mucus and on several sugars present in mucus compared to E. coli MG1655 ΔflhD but grows 30% faster on galactose. Moreover, E. coli MG1655 mot-1 and E. coli MG1655 ΔflhD appear to colonize equally well in one intestinal niche, but E. coli MG1655 mot-1 appears to use galactose to colonize a second, smaller intestinal niche either not colonized or colonized poorly by E. coli MG1655 ΔflhD. Evidence is also presented that E. coli MG1655 is a minority member of mixed bacterial biofilms in the mucus layer of the streptomycin-treated mouse intestine. We offer a hypothesis, which we call the "Restaurant" hypothesis, that explains how nutrient acquisition in different biofilms comprised of different anaerobes can account for our results.     

Histidine-Rich Glycoprotein Modulation of Immune/Autoimmune, Vascular, and Coagulation Systems

Histidine-rich glycoprotein (HRG) is plasma glycoprotein that has a multidomain structure, interacts with many ligands, and exhibit many modulatory functions in diverse biological systems. HRG ligands include Zn2+, tropomyosin, heparin and heparan sulphate, plasminogen, plasmin, fibrinogen, thrombospondin, IgG, FcgR, and complement. In many cases, the histidine-rich region of the molecule enhances ligand binding after interaction with Zn2+ or exposure to low pH, conditions associated with sites of tissue injury or tumor growth. The multidomain nature of HRG and diverse ligand binding properties indicates that it can act as an extracellular adaptor protein, bridging together different ligands mainly on cell surfaces. Apart from cell surface molecules, HRG can differentially target IgG, preventing generation of insoluble immune complexes. HRG binds to most cells primarily via heparan sulphate proteoglycans. HRG can enhance clearance of apoptotic and necrotic phagocytes as well as immune complexes. The anti-angiogenic properties of HRG are well established in vitro and in vivo. HRG can modulate other physiological processes such as cell adhesion and migration, fibrinolysis and coagulation, complement activation. This review presents an update on the molecular, structural, biological, and clinical properties of HRG and associated autoimmunity conditions.     

The effects of irritation at various levels of the airway upon tracheal mucus secretion in the cat.

1. Sulphated glycoprotein output from the trachea, isolated in situ, has been measured in anaesthetized cats by a radio-isotopic method. The effects of irritation of various parts of the airway on this mucus output were studied. 2. Mechanical stimulation of the nose and nasopharynx increased tracheal mucus output by reflexes which involved parasympathetic and probably also sympathetic motor pathways. 3. Laryngeal stimulation had a similar through the same motor pathways. 4. Inhalation of ammonia vapour into the lower airways reflexly increased mucus output from the isolated trachea. The efferent pathway for this reflex was mainly or entirely parasympathetic. It is argued that the afferent pathway involved cough receptors. 5. Lung inflation, inhalation of histamine aerosol and intravenous injection of phenyl diguanide (which excite mainly lung stretch receptors, lung 'irritant' receptors and alveolar 'J-receptors' respectively) had no consistent effect on tracheal mucus secretion. 6. The afferent and efferent pathways of these reflexes are discussed.     

Room for a role for radon in lung cancer causation?

Reduced ventilation due to energy saving has focussed interest on a potential lung cancer risk from increased indoor concentrations of alpha-emitting radon and radon daughters, escaping from building materials and from the ground. Some preliminary studies now also indicate a hazard to be present as related to radon daughter exposure in homes. However, the indoor radon daughter levels have probably been continuously increasing for half a century, especially in colder climates, due to the introduction of central heating instead of stoves and open fire places, reducing thermal ventilation. Furthermore, in our time, many people have got additional exposure through extended indoor work time instead of earlier outdoor activities in farming etc. The steeply increasing lung cancer rates over the past decades as well as the various oddities affecting the relationship between smoking and lung cancer, e.g. the urban-rural difference in lung cancer risk, also after standardization for smoking, the influence of immigration on lung cancer morbidity as well as the varying rates over the world and other observations, would obtain simple explanations by taking radon daughter exposure into account in addition to smoking. Then, also some curious and hitherto unexplained "inverse" relationships between lung cancer and inhalation of cigarette smoke or bronchitis in air-polluted areas, respectively, would become understandable.     

Breakdown of gastric mucus in presence of Helicobacter pylori.

The potential of Helicobacter pylori to degrade gastric mucus was examined. Colonies of H pylori cultured from antral mucosal biopsy specimens of patients with non-autoimmune gastritis were washed with sterile saline, passed through a sterilisation filter, and the filtrate examined for urease, protease, and mucolytic activity. The filtrate failed to hydrolyse bovine serum albumin, or to degrade stable mucus glycoprotein structures of high particle weight that had been separated from human gastric mucus on Sepharose 2B. The high particle weight mucus glycoprotein was, however, extensively degraded when incubated with H pylori filtrate (which possessed urease activity) in the presence of 2 M urea, to release fragments of Mr approximately 2 X 10(6). The high particle weight mucus glycoprotein was also broken down to a comparable extent when incubated with Jack bean urease in the presence of 2 M urea, or 1 M ammonium carbonate, or 40 mM carbonate-bicarbonate buffer (pH 8.7), but not when treated with 4 M urea alone, or Jack bean urease alone. These results indicate that the loss of high particle weight mucus glycoprotein in gastric mucus from patients with gastritis and gastric ulcers is unlikely to be due to the mucolytic action of an extra-cellular protease produced by H pylori, but it may result from the destabilising effects of a carbonate-bicarbonate buffer, generated at the mucosal surface when H pylori urease hydrolyses transuded plasma urea.     

Binding of Yersinia enterocolitica to rabbit intestinal brush border membranes, mucus, and mucin.

Mucus and its gel-forming glycoprotein component, mucin, are thought to protect the gastrointestinal tract from enteric pathogens by inhibiting their attachment to enterocytes. In this study, we investigated interactions between Yersinia enterocolitica (isogenic strains of virulent and nonvirulent organisms) and crude mucus, highly purified mucin, and brush border membranes (BBMs) isolated from the upper mid-, and distal small intestine and the proximal colon of the rabbit. Adherence of radiolabeled bacteria was assessed to BBMs, mucus, and mucin immobilized in polystyrene microtiter plate wells. Virulent Y. enterocolitica showed saturable binding to mucus, mucin, and BBMs from all four regions of the intestinal tract, although adherence to BBMs was appreciably greater than that to mucus or mucin. Maximal binding of bacteria was higher to BBMs from the distal small intestine and the proximal colon than to those from the upper and mid-small intestine, which may in part explain why the organism localizes to the ileo-caecal regions of the gut. Adherence of virulent Y. enterocolitica to BBMs was significantly reduced in the presence of homologous mucus or mucin preparations. Binding of virulent bacteria appears to depend on plasmid-encoded proteins located on the outer surface membrane, since (i) the isogenic strain lacking the virulence plasmid showed markedly less binding to all BBM, mucus, and mucin preparations; (ii) growth of the virulent strain at 25 degrees C, which inactivates its plasmid, significantly diminished binding to BBMs, mucus, and mucin; and (iii) mild proteolysis substantially decreased adherence of virulent bacteria to BBMs. Compared with rabbit intestinal and colonic mucins, binding of virulent Y. enterocolitica was significantly greater to purified human intestinal mucin and significantly less to rat intestinal mucin. These findings provide support for the role of mucus and mucin in host defense by preventing adherence of virulent Y. enterocolitica to epithelial cell membranes.     

Detection of antibodies directed against the cytoplasmic region of the human acetylcholine receptor in sera from myasthenia gravis patients

The nicotinic acetylcholine receptor (AChR) is the autoantigen in the human autoimmune disease myasthenia gravis (MG). Anti-AChR antibodies in MG sera bind mainly to conformational epitopes, therefore the determination of their specificities requires the use of native AChR. Antibody competition studies suggest that most MG antibodies are directed against the extracellular part of the molecule, whereas antibodies directed against the cytoplasmic region of the AChR have not been detected. To determine whether even small quantities of such antibodies exist in MG sera, we performed competition experiments based on the inhibition by MG sera of the binding of MoAbs to the human AChR, rather than inhibition by MoAbs of the binding of MG sera performed earlier. When MoAbs directed against cytoplasmic epitopes on the alpha or beta subunits (alpha 373-380 and beta 354-360) were used as test MoAbs, 17% or 9% of MG sera inhibited the binding of the anti-alpha or anti-beta subunit MoAbs, respectively, by > or = 50%. Non-specific inhibition was excluded. These results suggest the presence, in several MG sera, of antibodies directed against cytoplasmic regions of the AChR; yet these antibodies seemed to represent a relatively small proportion of the total anti-AChR antibodies. The corresponding epitopes may be involved in the inducing mechanisms in certain MG cases, and knowledge of the presence of such antibodies may be useful in understanding the autoimmune mechanism involved in MG.     

Accuracy of clinical diagnosis of lung cancer in Budapest in an institute specializing in chest diseases

Among 250 consecutive autopsies (170 males and 80 females) performed at the Institute of Pulmonology in Budapest in 1996/7, there were 132 deaths in which cancer of the lung/bronchus was deemed to be the underlying cause of death. At autopsy, six cases previously thought to be dying from lung cancer were found to have died from other diseases (false positive rate = 5%). Twelve lung cancer deaths were also found to have been missed, a false negative rate of 9%, which was similar for adenocarcinoma, squamous carcinoma, and small cell carcinoma cases. Our findings confirmed the expectation expressed earlier that death certification of lung cancer would be more accurate in an institute specializing in chest diseases, to which patients had to be fit enough to be transferred, than in two general hospitals in Budapest. Nevertheless, since most cases certified as dying from lung cancer die without the benefits available in the specialized institute, the estimated false negative and positive rates for lung cancer death certification in Hungary remain high, at an estimated 56% and 30%, respectively. The much lower autopsy rates in most other countries than in Hungary points to there being considerable inaccuracy in lung cancer mortality rates internationally.     

Direct transfer of p65 into T lymphocytes from systemic lupus erythematosus patients leads to increased levels of interleukin-2 promoter activity

Patients with allergic asthma present clinically with chronic or intermittent disease caused by either persistent or periodic allergen exposure. We sought to generate clinically relevant disease in mice, which would reflect the relapsing, remitting, and constant nature of this syndrome. We generated and compared acute onset, remission, relapse, and overt phases of the disease and found that acute disease was characterized by airway hyperreactivity, eosinophilic lung inflammation, excessive mucus production, and antigen-specific antibody and was rapidly followed by a remission. Mice rechallenged with aerosol antigen during the remission or treated with repeated aerosol challenges developed relapse and overt disease, respectively. Recurrent antigen exposure induced a progressive increase in bronchoalveolar lavage fluid immunoglobulin, mucus production, and a change in inflammatory infiltrates indicating a transition from acute to chronic inflammation. These data demonstrate distinct phases of disease representing a clinical spectrum of experimental allergic asthma and may have important implications for new treatment strategies.     

Comparative studies on neutralisation of primary HIV-1 isolates by human sera and rabbit anti-V3 peptide sera.

IgG binding to V3 peptides and serum neutralising responses were studied in four HIV-1 infected individuals with progressive disease over a period of 31-70 months. The 18-20 mer peptides comprised residues 299-317 (numbering of HIV1 MN) in the N-terminal half of the V3 loop of the envelope glycoprotein gp120 and were derived from the sequences of autologous, as well as heterologous isolates. All four individuals studied lacked anti-V3 IgG binding to at least one autologous V3 sequence. V3 peptides to which autologous sera lacked binding IgG were all immunogenic in rabbits and induced antisera that were broadly cross-reactive by EIA and broadly cross-neutralising to primary HIV-1 isolates. This indicates that the peptides are immunogenic per se and that the respective human hosts have selective defects in recognising the corresponding V3 sequences. Despite the absence of antibody binding to autologous V3 peptides, the human sera had neutralising antibodies to autologous (three out of four cases), as well as heterologous isolates (all cases). Moreover, in vitro exposure of the patients' isolates to autologous neutralising serum or the homologous rabbit antiserum selected for variants with amino acid substitutions close to the crown of the V3 loop or in regions outside the sequence corresponding to peptides used for immunisation. The amino acid exchanges affected V3 positions known to be antigenic and which are also prone to change successively in infected persons. It is likely that neutralising antibodies recognise both linear and conformational epitopes in the V3 loop. Apparently, there are several, but restricted, numbers of ways for this structure to change its conformation and thereby give rise to neutralisation resistant viruses.     

Distribution of polonium-210 in pulmonary tissues of cigarette smokers

Concentrations of the alpha-particle-emitting radioactive element polonium was measured in various pulmonary tissues of smokers and nonsmokers in order to determine 1) whether this radiation exposure is associated with the development of bronchial cancer in smokers; and 2) how smoke is absorbed and excreted in human lungs. Lung specimens from 25 current cigarette smokers, 2 current pipe smokers, 1 former cigarette smoker, and 8 nonsmokers ere analyzed. The average concentration of polonium in the peripheral parenchyma of current smokers was .0074 picocurie/gm and in nonsmokers was .0016. For smokers, the average concentration was doubled in more centrally located parenchyma and was greater in the upper than in the lower lobes. Polonium concentrations correlated with daily cigarette consumption but not with total cigarettes smoked. The concentrations in peribronchial lymph nodes of smokers were also higher than in nonsmokers. These values show no correlation with total or daily cigarette consumption. Polonium concentration was similiar in bronchial wall parenchyma as in lung parenchyma but was greater in bronchial epithelium than in parenchymal or lymph nodes. The patterns of distribution of polonium throughout the lung suggest that most inhaled smoke particles are rapidly cleared from the lung, and polonium is primarily cleared by mucus sheet. Since the highest local concentrations of polonium were found in bronchial epithelium from segmental bifurcations, leading to a high cumulative local radiation dose, polonium may be implicated in the initiation of bronchial cancer in humans.     

Identification of a 185 kd Maclura pomifera agglutinin binding glycoprotein as a candidate for a differentiation marker for alveolar type II cells in adult rat lung.

In adult rat lung the lectin Maclura pomifera agglutinin (MPA) binds apically to alveolar type II (ATII) cells but not to alveolar type I (ATI) cells. This suggests that the presence of MPA binding glycoproteins might be a criterion by which to distinguish the differentiated state of these two adult alveolar epithelial cells. The authors therefore studied MPA binding glycoproteins of ATII cells, comparing, biochemically and cytochemically, MPA binding glycoproteins in freshly isolated ATII cells with those in cultures of ATII cells that are "dedifferentiating" or have "dedifferentiated" as a result of growth on tissue culture plasticware. A MPA binding glycoprotein (185 kd) that is present in freshly isolated "differentiated" ATII cells and then is subsequently lost as isolated ATII cells "dedifferentiate" in tissue culture has been identified. This 185 kd MPA binding glycoprotein alone, or expressed in conjunction with other proteins, is a candidate for a differentiation marker for ATII cells. Preliminary data suggests that this 185 kd MPA binding glycoprotein is not found in ATI cells.