LUNG-SPECIFIC TRANSGENIC EXPRESSION OF KC ENHANCES RESISTANCE TO KLEBSIELLA-PNEUMONIAE IN MICE

A vigorous host response is required to effectively clear pathogenic b acteria from the lungs and is dependent upon the recruitment and activ ation of neutrophils and macrophages. A family of chemotactic cytokine s, referred to as chemokines, have been shown to participate in this c omplex protective response, In this study, we assessed the role of the C-X-C chemokine KC in lung antibacterial host defense using wild-type (wt) B6D2 mice or transgenic mice that had been bred on a B6D2 backgr ound expressing KC under the control of a Clara cell-specific promoter within the lung. The administration of Klebsiella pneumoniae to both wt and KC-transgenic mice resulted in a time-dependent expression of K C protein within the lung that peaked at 24 to 48 h postinoculation, W hen infected with K. pneumoniae, the KC-transgenic mice showed a strik ing improvement in survival compared with wt control mice. This improv ed survival was due to an increase in bacterial clearance, which occur red in association with a vigorous recruitment of neutrophils in the K C-transgenic mice compared with their wt control counterparts, No diff erences in the lung levels of the specific cytokines TNF-alpha, IFN-ga mma, IL-12, and IL-10 were noted. However, inducible macrophage inflam matory protein-2 levels were significantly decreased in the KC-transge nic mice compared with the wt mice, This study indicates that the comp artmentalized overexpression of KC in vivo results in increased lung b acterial clearance and improved survival, which occurs in association with enhanced polymorphonuclear leukocyte influx to the lung.