Laryngeal Epithelial Defenses against Laryngopharyngeal Reflux: Investigations of E-Cadherin, Carbonic Anhydrase Isoenzyme III, and Pepsin

Objectives: This is the third annual report of an international research network studying the cellular impact of laryngopharyngeal reflux (LPR) on laryngeal epithelium. The objective of this study was to investigate the presence of E-cadherin (epithelial cadherin; the intercellular junctional complex protein) in relation to the presence of (intracellular) pepsin and carbonic anhydrase isoenzyme III (CAIII). Methods: Fifty-four laryngeal biopsy specimens from 18 LPR patients were studied by immunohistochemistry and Western blotting for pepsin, E-cadherin, and CAIII. These data were compared to those from normal control subjects analyzed in another research study. Results: Intracellular pepsin was detected in LPR patients, but not in controls. E-cadherin expression was reduced in patients with LPR. Carbonic anhydrase III expression was not found in the vocal fold or in the majority of samples taken from the ventricle of LPR patients and was inversely associated with E-cadherin membranous expression. Conclusions: The findings of depleted E-cadherin and CAIII and the presence of pepsin appear to correlate with LPR. The reduced protective response indicated by the reduced expression of CAIII may play an important role in the disruption of the intercellular barrier associated with the down-regulation of E-cadherin.

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Biomarkers and laryngopharyngeal reflux

The Journal of Laryngology & Otology ◽

10.1017/s0022215111002234 ◽

2011 ◽

Vol 125 (12) ◽

pp. 1218-1224 ◽

Cited By ~ 31

Author(s):

J M Wood ◽

D J Hussey ◽

C M Woods ◽

D I Watson ◽

A S Carney

Keyword(s):

Carbonic Anhydrase ◽

Clinical Diagnosis ◽

Laryngopharyngeal Reflux ◽

Mucosal Injury ◽

Therapeutic Interventions ◽

Comprehensive Model ◽

Carbonic Anhydrases ◽

Carbonic Anhydrase Iii ◽

Mucin Expression ◽

E Cadherin

AbstractLaryngopharyngeal reflux is a controversial but increasingly made diagnosis used in patients with a collection of often non-specific laryngeal symptoms. It is a clinical diagnosis, and its pathophysiology is currently poorly understood.Previous reflux research has focused on injurious agents, acid, pepsin and biomarker expression. Failure of intrinsic defences in the larynx may cause changes in laryngeal epithelia, particularly alterations in carbonic anhydrases and E-cadherin. Carbonic anhydrase III levels vary in the larynx in response to laryngopharyngeal reflux, depending on location. Expression of E-cadherin, a known tumour suppressor, is reduced in the presence of reflux. Mucin expression also varies according to the severity of reflux.Further research is required to define the clinical entity of laryngopharyngeal reflux, and to identify a definitive mechanism for mucosal injury. Understanding this mechanism should allow the development of a comprehensive model, which would enable future diagnostic and therapeutic interventions to be developed.

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Immunohistochemical localization of carbonic anhydrase III in the pancreas of the monkey.

The Japanese Journal of Veterinary Science ◽

10.1292/jvms1939.51.642 ◽

1989 ◽

Vol 51 (3) ◽

pp. 642-645

Author(s):

Toshiho NISHITA ◽

Masao ASARI ◽

Hidetoshi OSHIGE ◽

Hiroharu MATSUSHITA ◽

Yutaka KANO

Keyword(s):

Carbonic Anhydrase ◽

Immunohistochemical Localization ◽

Carbonic Anhydrase Iii

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Muscle carbonic anhydrase III levels in normal and muscular dystrophia afflicted chickens

Acta Veterinaria Scandinavica ◽

10.1186/1751-0147-54-34 ◽

2012 ◽

Vol 54 (1) ◽

Cited By ~ 3

Author(s):

Toshiho Nishita ◽

Daisuke Yorifuji ◽

Kensuke Orito ◽

Nobutsune Ichihara ◽

Kazuyoshi Arishima

Keyword(s):

Carbonic Anhydrase ◽

Carbonic Anhydrase Iii

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Loss of Membrane Expression of E-Cadherin in Leukemic Erythroblasts

Archives of Pathology & Laboratory Medicine ◽

10.5858/2001-125-0198-lomeoe ◽

2001 ◽

Vol 125 (2) ◽

pp. 198-201

Author(s):

Geza Acs ◽

Virginia A. LiVolsi

Keyword(s):

Bone Marrow ◽

Bone Marrow Biopsy ◽

Bone Marrow Aspirate ◽

Hematopoietic Cells ◽

Immunoperoxidase Staining ◽

Membrane Expression ◽

Biopsy Specimens ◽

Erythroid Precursors ◽

Adhesive Interactions ◽

E Cadherin

Abstract Context.—The special societal relationships existing between various cell types in bone marrow suggests that there may be a link between the adhesive characteristics of hematopoietic cells and their maturation. Egress of the developing hematopoietic cells is also a highly regulated process governed by adhesive interactions. In leukemia, immature blasts are not retained within the marrow, suggesting a breakdown of adhesive mechanisms. Recent reports suggest that E-cadherin, an epithelial adhesion molecule, is expressed on erythroid precursors and megakaryocytes, but not on other hematopoietic marrow elements. Objective.—To characterize the expression pattern of E-cadherin in normal and leukemic erythroid precursors by immunohistochemistry in paraffin-embedded tissue and bone marrow aspirate smears. Methods.—Five normal bone marrow specimens from rib resections, 15 trephine bone marrow biopsy specimens, and 6 bone marrow aspirate smears from the iliac crest of patients with no known leukemia were selected. Fourteen bone marrow biopsy specimens from patients with erythroleukemia were also studied. Immunoperoxidase staining of paraffin-embedded tissue and air-dried aspirate smears for E-cadherin (1:200 dilution, HECD-1 clone) was performed using the avidin-biotin peroxidase technique. Results.—In paraffin-embedded bone marrow biopsy and rib specimens and in air-dried bone marrow aspirate smears, strong membrane expression of E-cadherin was seen in the normal erythroid precursors in all cases. In contrast, no membrane expression of E-cadherin was present in any of the bone marrow biopsy specimens from patients with erythroleukemia. Conclusions.—Immunohistochemical detection of membrane expression of E-cadherin may be a useful tool for identification of erythroid precursors. Cells of erythroleukemia lack membrane expression of E-cadherin, in contrast to their normal counterparts. Further studies are needed to define the potential role of E-cadherin in the maturation of erythroid precursors and to ascertain the significance of loss of membrane expression of E-cadherin in erythroleukemia.

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