NEUTRALIZATION OF MACROPHAGE INFLAMMATORY PROTEIN-2 ATTENUATES NEUTROPHIL RECRUITMENT AND BACTERIAL CLEARANCE IN MURINE KLEBSIELLA PNEUMONIA

The role of macrophage inflammatory protein-2 (MIP-2) in bacterial pne umonia was characterized. Mice were challenged with Klebsiella pneumon iae intratracheally, and organs were harvested at 8, 24, and 48 h. Ino culation with K. pneumoniae resulted in the time-dependent expression of MIP-2 mRNA and protein within the lung, which was maximal 48 h afte r inoculation. Mice were then passively immunized with rabbit anti-mur ine MIP-2 serum intraperitoneally 2 h before administration of K. pneu moniae. Treatment with anti-MIP-2 serum resulted in a 60% decrease in lung neutrophil (PMNL) influx and a significant increase in K. pneumon iae colony-forming units in both lung and liver homogenates. Finally, treatment with anti-MIP-2 serum decreased early (48-72 h) but not late (after 72 h) survival in animals with Klebsiella pneumonia. This stud y indicates that MIP-2 is produced during Klebsiella pneumonia and inh ibition of MIP-2 bioactivity in vivo results in decreased PMNL influx and lung bacterial clearance in murine Klebsiella pneumonia.