Mucin genes in horse airways: MUC5AC, but not MUC2, may play a role in recurrent airway obstruction

Abstract

Summary Reasons for performing study: Increased mucin gene expression may be an important cause of mucus accumulation observed in recurrent airway obstruction (RAO)‐affected horses. To date, however, no mucin gene sequences are available for the horse. Objectives: To identify equine homologues of gel‐forming mucins and investigate their expression at different airway generations of healthy and RAO‐affected horses. Methods: Two equine homologues were identified by cloning and sequencing fragments of equine (eq)MUC5AC and eqMUC2. Results: Semiquantitative RT‐PCR on RNA from airways (generations 1, 5, 10, 15; small airways and parenchyma), stomach (glandular), and colon revealed that eqMUC5AC is expressed in equine stomach and in all of the airway samples. In contrast, eqMUC2 steady‐state mRNA levels were detected in colon and very faintly in stomach, but not in airway tissue. EqMUC5AC expression was also compared to that of ZO‐1, a tight junction protein, and eqMUC5AC/ZO‐1 ratios were higher in RAO‐affected compared to control horses at all airway generations. Conclusions: That eqMUC5AC is expressed in horse airways, but any expression of MUC2 is undetectable and unlikely to be of physiological consequence. Potential relevance: EqMUC5AC up‐regulation may be a primary mechanism responsible for mucus hypersecretion and accumulation in RAO.

Air Quality in Horse Stables

“…The cytokine IL-6 is a pre-inflammatory marker and indicator for exposure to stable environment per se. It has also been shown to be associated with increased mucous secretion (Chen et al, 2003;Gerber et al, 2003). Therefore, a decreased amount of mucous in trachea together with a lower expression of IL-6 mRNA in BAL cells may indicate improvement of horse airway health after intervention.…”

“…In the search for potential allergens involved in RAO, an intra-dermal skin test and serum IgE analysis have been evaluated, but these have not proven to be clinically reliable in horses (Lorch et al, 2001;Lebis et al, 2002). Bronchial brushings, BAL, tracheal lavage, exhaled breath condensate, and even lung tissue samples have been shown to be of value in the investigation of the inflammatory process in the equine lung (Bureau et al, 2000;Gerber et al, 2003;Wyse et al, 2005). Imaging techniques, such as radiographic examination of equine lung, however, have shown to be of little value for the diagnosis of lower grade inflammation (Mazan et al, 2005).…”

Air Pollution and Domestic Animals

“…Just recently Ramseyer et al (2007) provided very strong evidence of an inherited predisposition to RAO on the basis of findings in two groups of horses. The same research group could demonstrate that mucin genes are likely to play a role too (Gerber et al, 2003b) and that the IL4RA gene located on chromosome 13 is a candidate for RAO predisposition . The results gathered so far suggest that RAO seems to be a polygenic disease.…”

Recurrent airway obstruction in horses - an allergic inflammation: a review

“…Additionally, IL-17 stimulates the expression of MUC5AC which may contribute to mucus hypersecretion in horses with chronic heaves. (Gerber et al, 2003).…”

“…Moreover, the observed Bcl-2 expression throughout the airways of RAOaffected horses is considered evidence that RAO is a condition that affects the whole tracheobronchial tree and is not limited to the peripheral airways. In addition, Bcl-2-positive mucous cells may synthesize more eqMUC5AC per cell than Bcl-2-negative cells, which may contribute to the hypersecretion of mucins (Gerber et al, 2003); therefore, two distinct populations of mucous cells may exist in RAO-affected horses. Bcl-2-positive mucous cells may represent mucous cells that are capable of synthesizing mucus at a faster rate than Bcl-2-negative cells (Bartner et al, 2006).…”