Indeed, recent studies have demonstrated that hCLCA1 may act as an Evofosfamide 918633-87-1 innate immune signaling molecule which activates airway macrophages and thereby enhances pro-inflammatory cytokine release . Moreover, asthmatic mice treated with antimCLCA3-antibodies showed remarkable reduction of airway inflammation. So far, only models of chronic and allergic airway inflammation and acute inflammation due to LPS have been characterized in mCLCA3-deficient mice. However, acute bacterial infection appears more suitable to test for a role of mCLCA3 in modulating innate immune responses. Besides septicemia, skin and soft tissue infections, S. aureus causes lower respiratory tract infections in humans, especially in infants and young children with CF. Here, we hypothesized that mCLCA3 has an impact on the innate immune response in acute S. aureus infection of the lung. mCLCA3-deficient mice and wild-type littermates were infected with S. aureus and the course of pneumonia was analyzed in comparison with uninfected mice regarding clinical signs, bacterial clearance, leukocyte immigration and cytokine response in bronchoalveolar lavage fluid, pulmonary vascular permeability, histopathology including morphometry, mucus cell quantification and respiratory tract mRNA expression levels of selected genes of interest, including mClca1 to 7, Muc5ac, Muc5b, Muc2, Cxcl-1, Cxcl-2 and Il-17. We show that mCLCA3 modulates the cellular leukocyte recruitment via IL-17 and CXCL-1 in bacterial pneumonia and thus appears to have an impact on the early innate immune response following S. aureus lung infection. The altered lung tissue was colored deeply red and, in few cases, visible accumulations of suppurative exsudate were present within the pneumonic areas. Histologically, infected lungs from both genotypes showed a moderate to severe, acute, multifocal, necro-suppurative bronchopneumonia with prominent perivascular edema, multifocal hemorrhage and massive accumulation of neutrophils and macrophages in the consolidated areas. S. aureus was detected by immunohistochemistry using a specific anti-S. aureus antibody exclusively in infected animals mostly within macrophages and neutrophils at each investigated time point. For semiquantification of histologic lesions, total affected lung areas were determined. Additionally, for evaluation of severity, several parameters were defined and a lung inflammation score was assessed. No differences between genotypes, neither in severity nor in expansion of lung lesions were observed at indicated time points in S. aureus infected mice. Only mild infiltration by macrophages close to the hilum of the lungs was observed in uninfected controls independently of genotype, likely due to the application of PBS. To examine the lung as a 3-dimensional structure and to warrant complete measurement of lung lesions, volume was estimated by Cavalieri principle in S. aureus infected lungs. Whole left lungs were cut into consecutive sections of equal thickness and each seventh slide was analyzed at indicated time points.