CCSP modulates airway dysfunction and host responses in an Ova-challenged mouse model

Abstract

Clara cell secretory protein (CCSP) is synthesized by nonciliated bronchiolar cells in the lung and modulates lung inflammation to infection. To determine the role of CCSP in the host response to allergic airway disease, CCSP-deficient [(-/-)] mice were immunized twice with ovalbumin (Ova) and challenged by Ova (2 or 5 mg/m(3)) aerosol. After 2, 3, and 5 days of Ova aerosol challenge (6 h/day), airway reactivity was increased in CCSP(-/-) mice compared with wild-type [CCSP(+/+)] mice. Neutrophils were markedly increased in the bronchoalveolar lavage fluid of CCSP(-/-) Ova mice, coinciding with increased myeloperoxidase activity and macrophage inflammatory protein-2 levels. Lung histopathology and inflammation were increased in CCSP(-/-) compared with wild-type mice after Ova challenge. Mucus production, as assessed by histological staining, was increased in the airway epithelium of CCSP(-/-) Ova mice compared with that in CCSP(+/+) Ova mice. These data suggest a role for CCSP in airway reactivity and the host response to allergic airway inflammation and provide further evidence for the role of the airway epithelium in regulating airway responses in allergic disease.

Chronic Exposure to Beta-Blockers Attenuates Inflammation and Mucin Content in a Murine Asthma Model

“…Mucous metaplasia is a cardinal feature of the asthma phenotype that is thought to play a central role in death from asthma (24,25,31). Recent studies also suggest that mucin hypersecretion can contribute significantly to AHR (27,32,33). Thus, the finding that chronic administration of beta-blockers reduces mucin content in airway epithelial cells suggests a possible identification of a cell type involved in the decreased AHR that we previously observed (15).…”

Clara cells drive eosinophil accumulation in allergic asthma

“…Clara cells have previously been reported to secrete various factors that are involved in the protection and defence mechanisms of the lung. For example, CC10 and SP-D secreted by Clara cells play a protective role in asthma by inhibiting Th2 responses [10,30]. Pro-inflammatory mediators, such as acidic mammalian chitinase, are upregulated in Clara cells during Th2 inflammation and their inhibition ameliorates inflammation [31].…”

“…These features identify them as an important cell compartment linking innate and adaptive immune responses in the lungs. For example, Clara cells respond to activated Th2 cells via the IL-4 receptor [5], can differentiate into mucus-producing goblet cells [9] and secrete anti-inflammatory factors such as Clara cell secretory protein (CC10), which counter-regulates the Th2 response in asthma [10]. Clara cells are also able to metabolise and detoxify xenobiotics and toxic compounds such as naphthalene (NA) present in cigarette smoke, which enables their specific depletion as used in our study [11,12].…”

Maintenance and Repair of the Bronchiolar Epithelium

“…In the steady state, these cells secrete low-molecular-weight proteins and chemical mediators important in host defense. Apically secreted proteins function in immunoregulation (7)(8)(9), in protection from environmental agents (10,11), and potentially in coordination of mechanical activities such as mucociliary clearance (12). Facultative progenitor cells of the airway are also a source of mucus proteins important for bacterial clearance (13,14).…”