CD34 Differentially Regulates Contractile and Noncontractile Elements of Airway Reactivity

Abstract

Airway hyperresponsiveness (AHR), a major hallmark of asthma, results from alterations of contractile and noncontractile elements of airway reactivity. CD34 is a sialomucin that is expressed on various cells involved in asthma, such as eosinophils and airway smooth muscle precursors, highlighting its potential influence in AHR. To study the role of CD34 in regulating the contractile and noncontractile elements of AHR, AHR was induced by chronic exposure to house dust mite (HDM) antigen. To assess the role of CD34 on the contractile elements of AHR, airway reactivity and airway smooth muscle contractility in response to methacholine were measured. To assess CD34's role in regulating the noncontractile elements of AHR, a chimeric mouse model was used to determine the impact of CD34 expression on inflammatory versus microenvironmental cells in AHR development. Extracellular matrix production, mucus production, and mast cell degranulation were also measured. Whereas wild-type mice developed AHR in response to HDM, a loss of airway reactivity was observed in Cd34 mice 24 hours after the last exposure to HDM compared with naive controls. This was reversed when airway reactivity was measured 1 week after the last HDM exposure. Additionally, mast cell degranulation and mucus production were altered in the absence of CD34 expression. Importantly, simultaneous expression of CD34 on cells originating from the hematopoietic compartment and the microenvironment was needed for expression of this phenotype. These results provide evidence that CD34 is required for AHR and airway reactivity maintenance in the early days after an inflammatory episode in asthma.

Augmented Pla2g4c/Ptgs2/Hpgds axis in bronchial smooth muscle tissues of experimental asthma

“…g ., [ 14 ]), and the accumulated inflammatory cells, such as eosinophils ( e . g ., [ 15 ]), also release various mediators around the smooth muscle cells. Some of these autocrine/paracrine mediators affect transcriptional signaling in the cells of airway smooth muscle, resulting in an alteration of its function [ 12 , 16 – 19 ].…”

Update in Asthma and Airway Inflammation 2018

“…They also identified that this response was mediated by p38 MAP kinase and rho kinase signalling that may be amenable to pharmacological intervention [18]. Using a similar sensitization model, Lortie and colleagues [19] [20]. The mechanism(s) by which these cells contract and mediate airway hyperresponsiveness has also been examined recently using precision cut lung slices and Ojiaku and colleagues demonstrated that TGF-β1 may play an important role in mediating contractility via increasing basal and carbachol-induced bronchoconstriction [21] via a smad3 dependent mechanism.…”