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 pneumonia was characterized. Mice were challenged with Klebsiella pneumoniae intratracheally, and organs were harvested at 8, 24, and 48 h. Inoculation with K. pneumoniae resulted in the time-dependent expression of MIP-2 mRNA and protein within the lung, which was maximal 48 h after inoculation. Mice were then passively immunized with rabbit anti-murine MIP-2 serum intraperitoneally 2 h before administration of K. pneumoniae. Treatment with anti-MIP-2 serum resulted in a 60% decrease in lung neutrophil (PMNL) influx and a significant increase in K. pneumoniae 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 study indicates that MIP-2 is produced during Klebsiella pneumonia and inhibition of MIP-2 bioactivity in vivo results in decreased PMNL influx and lung bacterial clearance in murine Klebsiella pneumonia. MIP-2 is produced during Klebsiella pneumonia and inhibition of MIP-2 bioactivity in vivo results in decreased PMNL influx and lung bacterial clearance in murine Klebsiella pneumonia.
Greenberger
M J
MJ
Department of Medicine, University of Michigan Medical School, Ann Arbor, USA.
Strieter
R M
RM
Kunkel
S L
SL
Danforth
J M
JM
Laichalk
L L
LL
McGillicuddy
D C
DC
Standiford
T J
TJ
D000818:Animals; D016470:Bacteremia / Q000382:microbiology; D001483:Base Sequence; D054426:Chemokine CXCL2; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D015169:Colony Count, Microbial; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D007116:Immunization, Passive; D007124:Immunoenzyme Techniques; D007710:Klebsiella Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D007711:Klebsiella pneumoniae / Q000302:isolation & purification / Q000502:physiology*; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D015846:Monokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D009195:Peroxidase / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors
D054426:Chemokine CXCL2; D002630:Chemotactic Factors; D016207:Cytokines; D017931:DNA Primers; D015846:Monokines; D012333:RNA, Messenger; D009195:Peroxidase