Cutting Edge: Altered Pulmonary Eosinophilic Inflammation in Mice Deficient for Clara Cell Secretory 10-kDa Protein

Abstract

Clara cell secretory protein (CC10) is a steroid-inducible protein, and its in vivo function is currently unclear. The role of CC10 in modulation of pulmonary allergic inflammation was examined in mice deficient for the CC10 gene. Wild-type and homozygous CC10-deficient mice were sensitized with an Ag, OVA, and challenged with either OVA or saline. When compared with that seen in wild-type mice, a significantly higher level of pulmonary eosinophilia was found in Ag-sensitized and challenged CC10-deficient mice. Significantly increased levels of Th2 cytokines IL-4, IL-5, IL-9, and IL-13 were also found in CC10-deficient mice. In addition, an increased level of eotaxin, but not RANTES, was also seen in CC10-deficient mice. No significant difference was observed in the level of a Th1 cytokine, IFN-γ, between different groups of mice. These results provided the first in vivo evidence that CC10 plays a role in the modulation of pulmonary allergic inflammation.

Immobilized Lactoferrin Is a Stimulus for Eosinophil Activation

“…The capacity of immobilized lactoferrin to stimulate eosinophil superoxide production, degranulation, and leukotriene C 4 production suggests that lactoferrin adherent to the surface epithelium may constitute one mechanism for initiating these events within the airway. Moreover, the present results along with the activity of immobilized secretory IgA (16,17) and the finding that Clara cell secretory 10-kDa protein can limit eosinophil-associated lung inflammation (47) indicate that prominent constituents within the airway surface liquid may contribute to the regulation of eosinophil activation within the airway. Although concomitant neutrophil infiltration and activation within the lungs could constitute an additional source of lactoferrin for eosinophil activation, it is worth noting that oxidizing pollutants have been reported to increase lactoferrin synthesis by bronchial epithelial glands (48).…”

Keratinocyte growth factor-induced proliferation of rat airway epithelium is restricted to Clara cells in vivo

“…CC10-knockout mice exhibited an increased susceptibility to inhaled oxidant gases [52]. SINGH and KATYAL [34] suggested that CC10 may function as a regulator of inflammation in the lung, a notion which is still a matter of debate [28,[52][53][54][55]. CC10 was reported to be decreased in various conditions of inflammation [53,56,57], and deficiency in CC10 as a result of transgenic experiments or in humans with a chronic CC10 deficiency, e.g.…”

“…SINGH and KATYAL [34] suggested that CC10 may function as a regulator of inflammation in the lung, a notion which is still a matter of debate [28,[52][53][54][55]. CC10 was reported to be decreased in various conditions of inflammation [53,56,57], and deficiency in CC10 as a result of transgenic experiments or in humans with a chronic CC10 deficiency, e.g. in long-term cigarette smokers [58,59], appears to be characterised by a tendency towards an exaggerated inflammatory response [53,55], and may contribute to carcinogenesis [59].…”

Uteroglobin Suppresses SCCA Gene Expression Associated with Allergic Asthma

“…Both UG-KO and WT mice were maintained under germ-free conditions, and all experiments were performed according to an institutionally approved animal care and use protocol. The methodology for inducing airway inflammation by OVA is previously reported (3,4).…”

“…The founding member of the secretoglobin superfamily of proteins (2), UG, is constitutively expressed at a high level in the pulmonary mucosal epithelial cells of virtually all mammals including mice. We previously reported that compared with wild type (WT) littermates, the lungs of the UG-knock-out (UG-KO) mice express markedly higher levels of Th2 cytokines and manifest exaggerated airway inflammatory response to allergens marked by elevated levels of eosinophil infiltration (3,4). All of these are characteristically found in human airway inflammatory diseases such as bronchial asthma in which sensitivity to allergens play a critical pathogenic role.…”