Bcl-2 in LPS- and allergen-induced hyperplastic mucous cells in airway epithelia of Brown Norway rats

2000 ◽  
Vol 279 (6) ◽  
pp. L1210-L1217 ◽  
Author(s):  
Yohannes Tesfaigzi ◽  
Mark J. Fischer ◽  
Andrea J. Martin ◽  
Jeanclare Seagrave

Environmental toxins, infection, and allergens lead to a transient mucous cell hyperplasia (MCH) in airway epithelia; however, the mechanisms for reducing mucous cell numbers during recovery are largely unknown. This study investigated Bcl-2 expression in mucous cells induced by a neutrophilic or eosinophilic inflammatory response. Brown Norway rats intratracheally instilled with lipopolysaccharide (LPS) showed an inflammatory response characterized primarily by neutrophils. Secreted mucin was increased fourfold at 1 day, and the number of mucous cells was increased fivefold 2, 3, and 4 days post-LPS instillation compared with those in noninstilled rats. None of the mucous cells in non- or saline-instilled control animals expressed Bcl-2, whereas 20–30% of mucous cells were Bcl-2 positive 1 and 2 days post-LPS instillation. Brown Norway rats immunized and challenged with ovalbumin (OVA) for 2, 4, and 6 days showed an inflammatory response characterized primarily by eosinophils. Secreted mucin increased fivefold, and mucous cell number increased fivefold after 4 and 6 days of OVA exposure compared with water-immunized control rats challenged with OVA aerosols. Approximately 10–25% of mucous cells were Bcl-2 positive in OVA-immunized and -challenged rats. These data demonstrate Bcl-2 expression in hyperplastic mucous cells of Brown Norway rats regardless of the type of inflammatory response and indicate that apoptotic mechanisms may be involved in the resolution of MCHs.

2006 ◽  
Vol 291 (4) ◽  
pp. L602-L609 ◽  
Author(s):  
Lisa R. Bartner ◽  
N. Edward Robinson ◽  
Matti Kiupel ◽  
Yohannes Tesfaigzi

This study examined the contribution of delayed apoptosis of bronchial mucous cells to mucus accumulation in equine recurrent airway obstruction (RAO). In pilot studies, Bcl-2, an apoptosis inhibitor, was detected in airway mucous cells of RAO-affected horses in remission and during acute disease, when most mucus was secreted. To study whether delayed apoptosis results in an increase in the number of mucous cells during disease recovery, six RAO-affected and six control horses were fed hay for 5 days to induce inflammation and then pellets for 7 days to partially resolve RAO before euthanasia. RAO-affected horses had more airway obstruction and luminal mucus than control horses under both management systems. At the time of euthanasia, RAO-affected horses had more inflammation and Bcl-2-positive bronchial mucous cells than control animals. In horses with >10 and <10 neutrophils per microliter of bronchoalveolar lavage fluid, >50% and <10% of mucous cells stained positive for Bcl-2, respectively. No differences in mucous cell number or amount of stored mucosubstance were observed between RAO-affected and control horses, but in RAO-affected animals, the amount of stored mucosubstance decreased as the number of neutrophils in bronchoalveolar lavage fluid increased. Because the number of mucous cells was similar in both groups of horses but only mucous cells of RAO-affected horses expressed Bcl-2 during recovery from acute disease, a conclusive role for Bcl-2 in prolonging bronchial mucous cell life could not be determined. Future studies are needed to compare horses that are kept in remission for prolonged periods when all mucous cells are fully developed.


2004 ◽  
Vol 287 (2) ◽  
pp. L286-L295 ◽  
Author(s):  
Shawnessy D. Larson ◽  
Charles G. Plopper ◽  
Greg Baker ◽  
Brian K. Tarkington ◽  
Kendra C. Decile ◽  
...  

Mucous cell hypersecretion and increased neuropeptide production play a role in the exacerbation of symptoms associated with asthma. The source of these neuropeptides have been confined to the contributions of small afferent nerves or possibly neuroendocrine cells. We tested the hypothesis that repeated exposure to allergen would alter the sources and abundance of neuropeptides in airways. Right middle lobes from rats (8 wk old) exposed to 2.5% ovalbumin (OVA) for five episodes (30 min each) or filtered air were inflation fixed with paraformaldehyde. The lobes were dissected to expose the airway tree, permeabilized with DMSO, and incubated in antibody to rat calcitonin gene-related peptide (CGRP), followed with a fluorochrome-labeled second antibody. CGRP-positive structures were imaged via confocal microscopy. Airways were later embedded in plastic and sectioned for cell identification. In animals challenged with OVA, CGRP-positive cells, not neuroendocrine or neuronal in origin (confirmed by a lack of protein gene product 9.5 signal), were recorded along the axial path. In section, this fluorescent signal was localized to granules within epithelial cells. Alcian blue/periodic acid-Schiff staining of these same sections positively identify these cells as mucous cells. Mucous cells of animals not challenged with OVA were not positive for CGRP. We conclude that episodic allergen exposure results in the accumulation of CGRP within mucous cells, creating a new source for the release of this neuropeptide within the airway.


PLoS Genetics ◽  
2021 ◽  
Vol 17 (12) ◽  
pp. e1009969
Author(s):  
Yu-Fen Lu ◽  
Da-Wei Liu ◽  
I-Chen Li ◽  
Jamie Lin ◽  
Chien-Ming Wang ◽  
...  

Teleosts live in aquatic habitats, where they encounter ionic and acid-base fluctuations as well as infectious pathogens. To protect from these external challenges, the teleost epidermis is composed of living cells, including keratinocytes and ionocytes that maintain body fluid ionic homeostasis, and mucous cells that secret mucus. While ionocyte progenitors are known to be specified by Delta-Notch-mediated lateral inhibition during late gastrulation and early segmentation, it remains unclear how epidermal mucous cells (EMCs) are differentiated and maintained. Here, we show that Delta/Jagged-mediated activation of Notch signaling induces the differentiation of agr2-positive (agr2+) EMCs in zebrafish embryos during segmentation. We demonstrated that agr2+ EMCs contain cytoplasmic secretory granules and express muc5.1 and muc5.2. Reductions in agr2+ EMC number were observed in mib mutants and notch3 MOs-injected notch1a mutants, while increases in agr2+ cell number were detected in notch1a- and X-Su(H)/ANK-overexpressing embryos. Treatment with γ-secretase inhibitors further revealed that Notch signaling is required during bud to 15 hpf for the differentiation of agr2+ EMCs. Increased agr2+ EMC numbers were also observed in jag1a-, jag1b-, jag2a- and dlc-overexpressing, but not jag2b-overexpressing embryos. Meanwhile, reductions in agr2+ EMC numbers were detected in jag1a morphants, jag1b mutants, jag2a mutants and dlc morphants, but not jag2b mutants. Reduced numbers of pvalb8-positive epidermal cells were also observed in mib or jag2a mutants and jag1a or jag1b morphants, while increased pvalb8-positive epidermal cell numbers were detected in notch1a-overexpressing, but not dlc-overexpressing embryos. BrdU labeling further revealed that the agr2+ EMC population is maintained by proliferation. Cell lineage experiments showed that agr2+ EMCs are derived from the same ectodermal precursors as keratinocytes or ionocytes. Together, our results indicate that specification of agr2+ EMCs in zebrafish embryos is induced by DeltaC/Jagged-dependent activation of Notch1a/3 signaling, and the cell population is maintained by proliferation.


2008 ◽  
Vol 9 (3) ◽  
Author(s):  
Norbert Fülöp ◽  
Wenguang Feng ◽  
Dongqi Xing ◽  
Kai He ◽  
László G. Nőt ◽  
...  

2003 ◽  
Vol 33 (10) ◽  
pp. 1905-1914 ◽  
Author(s):  
Irina P Panyushkina ◽  
Malcolm K Hughes ◽  
Eugene A Vaganov ◽  
Martin AR Munro

We reconstructed air temperature for two periods in the growth season from cell dimension and cell number variability in cross-dated tree rings of Larix cajanderi Mayr. from northeastern Siberia. Thirteen tree-ring chronologies based on cell size, cell wall thickness, and cell number were developed for AD 1642–1993. No clear evidence was found of an age-related trend in cell dimensions in the sampled materials, but cell numbers were correlated with cambial age. The chronologies contain strong temperature signals associated with the timing of xylem growth. We obtained reliable reconstructions of mean June temperature from the total cell number and July–September temperature from the cell wall thickness of latewood. June temperature and July–September temperature covaried for most of the period from AD 1642 to AD 1978. After that time, June temperature became cooler relative to July–September temperature. This difference caused disproportional changes in earlywood tracheids because of the late start of growth and cool conditions in June followed by warming during the rest of the season. The identification of this unusual recent change has shown that intraseasonal resolution may be achieved by cell dimension and cell number chronologies.


2014 ◽  
Vol 135 ◽  
pp. 180-188 ◽  
Author(s):  
Robert L. Thunhorst ◽  
Terry Beltz ◽  
Alan Kim Johnson

1994 ◽  
Vol 93 (2) ◽  
pp. 464-469 ◽  
Author(s):  
Hideo Tsukagoshi ◽  
Tatsuo Sakamoto ◽  
Wenbing Xu ◽  
Peter J. Barnes ◽  
K.Fan Chung

2001 ◽  
Vol 8 (4) ◽  
pp. 762-767 ◽  
Author(s):  
R. de Waard ◽  
J. Garssen ◽  
J. Snel ◽  
G. C. A. M. Bokken ◽  
T. Sako ◽  
...  

ABSTRACT In this study, the effects of orally administered viableLactobacillus casei Shirota strain YIT9029 on the immunity parameters of Wistar and Brown Norway rats were examined. For this purpose, we used the Trichinella spiralis host resistance model. Two weeks before and during T. spiralisinfection, rats were fed 109 viable L. casei bacteria 5 days per week. The T. spiralis-specific delayed-type hypersensitivity (DTH) response was significantly enhanced in both Wistar and Brown Norway rats given L. casei. In both rat strains fedL. casei, serum T. spiralis-specific immunoglobulin G2b (IgG2b) concentrations were also significantly increased. In the model, no significant effects ofL. casei on larval counts or inflammatory reactions in the tongue musculature, body weights, or lymphoid organ weights were observed. Serum specific antibody responses, other than IgG2b, were not changed by feeding of L. casei. In contrast toL. casei, it was shown that orally administeredBifidobacterium breve or Bifidobacterium bifidum had no influence on the measured infection and immunity indices in the rat infection model. Since the rat DTH response is considered to be a manifestation of Th1 cell-mediated immunity and the IgG2b isotype has been associated with Th1 activity, it was concluded that Th1 cells could play an active role in the immunomodulatory effects of orally administered L. casei. Furthermore, our data do not indicate that the effect of oral supplementation withL. casei is dependent on the genetic background of the host.


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