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*
Departments of Medicine and Pediatrics, Divisions of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, MI 48109; and
Department of Immunology, Schering-Plough Research Institute, Kenilworth, NJ 07033
A vigorous host response is required to effectively clear
pathogenic bacteria from the lungs and is dependent upon the
recruitment and activation of neutrophils and macrophages. A family of
chemotactic cytokines, referred to as chemokines, have been shown to
participate in this complex 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 background 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 KC
protein within the lung that peaked at 24 to 48 h postinoculation.
When infected with K. pneumoniae, the KC-transgenic mice
showed a striking improvement in survival compared with wt control
mice. This improved survival was due to an increase in bacterial
clearance, which occurred in association with a vigorous recruitment of
neutrophils in the KC-transgenic mice compared with their wt control
counterparts. No differences in the lung levels of the specific
cytokines TNF-
, IFN-
, IL-12, and IL-10 were noted. However,
inducible macrophage inflammatory protein-2 levels were significantly
decreased in the KC-transgenic mice compared with the wt mice. This
study indicates that the compartmentalized overexpression of KC in vivo
results in increased lung bacterial clearance and improved survival,
which occurs in association with enhanced polymorphonuclear
leukocyte influx to the lung.
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