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T G Christensen

Publications and source records attributed to T G Christensen.

48 records · Page 3Linked to original sources
PubMed1982

An alternative model for the binding and release of diferric transferrin by reticulocytes.

The biphasic binding of diferric transferrin to reticulocytes has been reevaluated with a series of kinetic and equilibrium studies. Identical binding progress profiles were observed for reticulocytes in the presence or absence of oxygen. The relative size of the rapid initial adsorption step could be increased to ca. 65% of the total binding by stripping the cells of endogenous transferrin or reduced to 0% by preloading the cells with nonradiolabeled diferric transferrin. Preloading the cells with 125I-labeled diferric transferrin and chasing with 131I-labeled diferric transferrin revealed identical rate constants for release and binding. Scatchard plots of equilibrium binding of diferric transferrin to reticulocytes showed no significant effects of anaerobiasis or 2,4-dinitrophenol on the equilibrium binding constant or the maximum number of binding sites. The potent microtubule inhibitor nocodazole had no effect on the progress curves for transferrin binding or iron uptake by reticulocytes. It was concluded that the rapid adsorption step in the binding profile represents binding to open receptors and that the slow first-order binding phase represents binding of radiolabeled transferrin to receptors already occupied by nonlabeled endogenous transferrin as this endogenous transferrin leaves the receptors. Furthermore, this first-order binding phase, unlike iron uptake, does not require the presence of active oxidative phosphorylation. These findings are consistent with a specific desorption-adsorption model for the interaction of diferric transferrin with reticulocytes.

2,4-Dinitrophenol↗
PubMed1982

Endogenous peroxidase in the conducting airways of hamsters: morphologic evidence of synthesis and secretion.

The lower respiratory tract of the hamster was examined for evidence of endogenous peroxidase activity. Using the standard diaminobenzidine cytochemical technique with controls to distinguish peroxidase from other hemoproteins, brown peroxidase reaction product was observed in the tracheal lumen and within epithelial secretory cells. The lumen and secretory cells of submucosal glands also contained peroxidase activity. Peroxidase-positive cells were most numerous in the upper trachea. Activity gradually decreased distally so that the least number of positive cells occurred in the extrapulmonary bronchus. Older animals contained many more positive cells than did younger animals. Within the lung, all epithelial cell types in both conducting and respiratory zones lacked activity. Peroxidase-positive cells in the tracheo-bronchial epithelium were identified as mucous cells by electron microscopy. Within these cells, peroxidase activity was found in the nuclear envelope, cisternae of rough endoplasmic reticulum, Golgi saccules, condensing vacuoles, and secretory granules. Discharge of the granules into the lumen appeared to result from a merocrine type of secretion. These ultrastructural findings are similar to those described for the secretory peroxidase in mammary and salivary glands. The peroxidase in these glands plays a key role in a nonspecific antibacterial system. Although the function of airway peroxidase is presently unknown, it is quite possible that it too possesses anti-infectious properties, thus forming an important adjunct to the well-known physical, cellular, and immunologic processes that protect the respiratory tract from microbial and toxic injury.

Animals↗
PubMed1981

Ultrastructural localization of endogenous peroxidase in the lower respiratory tract of the guinea pig.

Endogenous peroxidase activity was demonstrated by cytochemistry in mucous cells of the submucosal glands and tracheobronchial epithelium of guinea pigs. It is localized in the nuclear envelope, in cisternae of rough endoplasmic reticulum, and in secretory granules. It was not seen in Golgi saccules or in the airway lumen. By contrast, all epithelial cells within the lung including mucous (goblet) cells lack activity. Reaction product is also absent from alveolar macrophages and mast cells. The appearance of peroxidase in mucous cells is age-related. No activity was seen at 1.5 ms of age. A few mucous cells were positive at 2.5 and 3 ms while the proportion of positive cells increased substantially up to 7 ms. Thus, the age of guinea pigs in HRP transport studies must receive careful consideration in order to avoid misinterpretation of results. The function of mucous cell peroxidase is unknown. The results of this study suggest that it is secreted. Whether it plays a significant role in lung defense through its well documented anti-infectious properties remains to be determined.

Aging↗
PubMed1979

Myointimal plaques in pulmonary vascular sclerosis associated with interstitial lung fibrosis.

In interstitial fibrosis of the lung, pulmonary vessels show priminent sclerotic changes. We have studied arteries in lung biopsies from patients with lung fibrosis of varied etiology using light and electron microscopy. It was found that the sclerotic change is essentially confined to arteries within fibrotic areas, areas of "nonfibrotic" lung having vessels with no intimal thickening. The changes are most striking in arteries with an external diameter of 500 micrometer. or greater (p less than 0.001), although smaller sized vessels also show significant changes. Ultrastructurally, the plaques are composed of typical smooth muscle cells with basement lamina, pinocytotic vesicles, dense bodies, and cytoplasmic microfilaments. These arterial changes could result from damage to the blood vessel which accompanies the mechanism producing lung fibrosis. Alternatively, the myointimal change could conceivably be part of an adaptive response following the establishment of fibrosis. In either instance, the narrowing would decrease blood flow to physiologically disadvantaged areas of the lung, and the muscle fibers might play an active role in reducing the blood flow.

Adult↗
PubMed1978

Bronchial mucus hypersecretion induced by elastase in hamsters: ultrastructural appearances.

Male golden hamsters were exposed to a solution of purified pancreatic elastase by intratracheal injection. They developed panlobular (panacinar) emphysema and, in addition, were found to show severe goblet cell metaplasia in the major bronchi. The metaplastic change in the respiratory epithelium was associated with persistence of a fenestrated sheet of mucus, widely present throughout the bronchial tree, which was greater in amount than that in either unexposed or saline exposed controls. Transmission electron micrography showed a striking increase in size of individual goblet cells, due to increased numbers of secretory droplets which were also much larger and paler than in control bronchi. Ciliated cells appeared smaller than normal due to compression by the swollen goblet cells. The presence of prominent dilatation of the endoplasmic reticulum and the increased frequency of secretory droplet release from the luminal surface stronly suggest that the goblet cell changes were due to increased formation and secretion of mucus into the damaged bronchi. These experiments show that a single exposure to elastase produces both severe panlobular emphysema and goblet cell metaplasia. The changes resemble several of the anatomic features of chronic obstructive lung disease in man for which this injury may be a suitable model.

Animals↗
PubMed1977

Irreversible bronchial goblet cell metaplasia in hamsters with elastase-induced panacinar emphysema.

A single intratracheal instillation of pancreatic elastase in hamsters induces a lesion resembling human panacinar emphysema. This paper reports the occurrence of irreversible goblet cell metaplasia in the bronchial epithelium of hamsters similarly exposed to elastase. The goblet cell change was dose related; a dose of 0.1 mg/100 g body wt or less at 16 days, produced slight or moderate goblet cell metaplasia in fewer than half the animals, whereas 84% of animals treated with a dose between 0.2 and 0.5 mg/100 g body wt developed goblet cell metaplastic lesions, more than half of which were considered to be severe. The percentage of goblet cells in the epithelium of elastase-treated hamsters (32.5) was significantly higher (P less than 0.005) than that of unexposed (12.2) and saline-exposed controls (18.7). All hamsters examined 6 and 12 mo after elastase treatment showed the lesion. The pathogenesis of the changes is unclear but the possibility is raised that the bronchial changes may be due to disturbance of an endogenous protease-antiprotease system. The findings suggest the hypothesis that, under appropriate circumstances, a single pulmonary insult in man could lead to a permanent lung injury demonstrating the anatomic lesions of both chronic bronchitis and panacinar emphysema.

Animals↗
PubMed1977

The hamster as a model of chronic bronchitis and emphysema in man.

Male hamster weighing 100-140 g were exposed to 50-500 microgram purified elastrase per 100 g body weight by intratracheal injection. The hamster were killed at intervals up to 12 months after treatment, and their lungs were examined grossly and microscopically. At 8 days after treatment, the lungs appeared to have a greater volume than the controls. At 16 days, the lungs remained inflated when the pleural cavity was opened. Alveolar size was increased in proportion to the dose of elastase. From 16 days onward, the emphysematous lesion was well established. The number of goblet cells in the bronchi also increased. Counts of goblet cells as a proportion of all bronchial lining cells showed that goblet cells more than doubled in number in elastase treated hamsters as compared with controls. The mechanism for the two lesions caused by elastase was not clear. It was concluded that the elastase treated hamster is a useful model for studies of the pathogenesis of chronic bronchitis and emphysema in man.

Animals↗
PubMedDate not supplied

Resistance of hamster bronchiolar epithelium to neutrophil elastase: investigation by cell surface lectin cytochemistry.

An intratracheal instillation of human neutrophil elastase (HNE) causes accumulation of an excess number of secretory granules in the epithelial secretory cells lining the hamster bronchus. This chronic lesion, which we refer to as secretory cell metaplasia (SCM), is not seen in the trachea or bronchioles. Because luminal cell surface lectin binding is much higher in the trachea than in the bronchus, we concluded that tracheal resistance may be due to a protective glycoconjugate coat. In the present ultrastructural study, we analyzed the lectin-binding capability of bronchiolar epithelial cells to determine whether their luminal cell surface glycoconjugate layer is similar to tracheal epithelial cells. None of the six ferritin-conjugated lectins showed higher binding in bronchioles compared to the bronchus, suggesting that a high level of surface oligosaccharides is not necessary for resistance to the metaplastic effects of HNE. HNE caused a significant reduction in bronchiolar surface binding of the gold-labeled, secretory cell-specific lectin, Helix pomatia agglutinin. The principal granulated secretory cell type in bronchioles was ultrastructurally similar to a form of bronchial Clara cell that converts to a mucous cell phenotype in response to HNE. The results suggest that absence of bronchiolar SCM is not attributable to a protective layer of cell surface oligosaccharides, a lack of cellular contact by HNE, or the presence of a morphologically distinct population of epithelial cells in bronchioles.

Animals↗
PubMedDate not supplied

Changes in the carbohydrate content of airway epithelium induced by human neutrophil elastase in the hamster.

Hamster airway epithelial secretory cells were investigated by light and electron microscopic cytochemistry to study possible changes in their carbohydrate content induced by human neutrophil elastase (HNE), an agent known to cause replacement of Clara cells by mucous cells in hamster bronchi. Characterization of secretory cell carbohydrates by the AB/PAS, PA-TCH-SP, HID-TCH-SP, and LID-TCH-SP sequences indicated the existence of periodate-reactive acidic glycoconjugates, but the absence of sulfated or carboxylated glycoconjugates in both treated and control animals. Differences were seen in the quality and quantity of historeactive carbohydrates throughout various regions in the lower respiratory tract. This was especially evident in the HNE-treated animals. It is concluded that the HNE-induced expression of the mucous cell phenotype is associated with an increase in the amount of neutral and acidic nonsulfated and noncarboxylated polysaccharides stored in the secretory granules of these cells.

Animals↗
PubMedDate not supplied

Elastase causes secretory discharge in bronchi of hamsters with elastase-induced secretory cell metaplasia.

A single intratracheal instillation of human neutrophil elastase (HNE) into hamsters causes granule discharge from bronchial secretory cells followed by marked accumulation of granules, visible by light microscopy at 21 days and persisting through 18 months. To determine whether persistence of this secretory cell metaplasia (SCM) is due to inability of the metaplastic secretory cells to secrete their granules, hamsters having HNE-induced SCM were challenged with the potent secretagogue HNE. Four groups of 10 hamsters each received 300 micrograms HNE intratracheally. Twenty-one days later, hamsters were intratracheally treated with HNE or saline; the groups were designated HNE-HNE and HNE-SAL, respectively. Hamsters were killed 2 h or 21 days following the second treatment. Using light microscopy, nucleated epithelial cells were counted in plastic sections of the left main intrapulmonary bronchus. Cells were classified as ciliated (C), basal (B), indeterminate (IN), or secretory. Secretory cells were subcategorized as S0 (0 granules), S1 (1-4 granules), S2 (> or = 5 granules with intervening cytoplasm), and S3 (abundant granules completely filling the cytoplasm). At 2 h, S3 cell frequency in the HNE-HNE group was 13.0 +/- 2.2 (% mean +/- SE), significantly lower than in the 2 h HNE-SAL group (31.1 +/- 4.5). Concomitantly, higher cell frequencies were seen in the other secretory categories of the HNE-HNE group compared to the HNE-SAL group; S2 17.1 +/- 1.9 compared to 9.4 +/- 1.9, S1 2.4 +/- 0.4 compared to 1.1 +/- 0.5, and S0 2.4 +/- 0.5 compared to 1.1 +/- 0.5, respectively. The S3 cell frequency of the 21-day HNE-HNE group was 25.4 +/- 4.7, increased significantly compared to the 2 h HNE-HNE group; this change was concomitant with significant decrease in the frequency of the S0 secretory cells. Cell frequencies of C, B, and IN were not affected by treatment or time. It is concluded that metaplastic secretory cells discharge their granules in response to HNE; SCM returns to its original state after HNE rechallenge; persistent SCM is not due to the inability of metaplastic secretory cells to discharge their granules.

Animals↗
PubMedDate not supplied

Abnormal mucous cell phenotype induced by neutrophil elastase in hamster bronchi.

Bronchial mucous cell metaplasia (MCM) is a histologic component of chronic mucus hypersecretion. The hamster model of elastase-induced MCM appears to involve an irreversible conversion of Clara cells to mucous cells. The present study questioned whether the mucous cells seen in hamster bronchi exposed to neutrophil elastase produce and maintain a form of glycoconjugate secretory product different from that normally found in mucous cells or Clara cells. Ultrastructural cytochemistry using the gold-labeled lectin HPA revealed a difference in the cell surface and stored secretory granules of elastase-derived mucous cells compared to normal mucous cells and Clara cells at 3 weeks and 4 months following exposure. The results suggest that elastase irreversibly alters the glycoconjugate character of the Clara cells normally present so that they produce an abnormal form of mucus. Because secreted glycoconjugates can affect the rate of mucociliary clearance and receptor-mediated binding of microorganisms, this change in phenotype may be involved in the pathogenesis of diseases associated with chronic mucus hypersecretion in humans.

Animals↗