Macrophage inflammatory protein-2 is a mediator of polymorphonuclear neutrophil influx in ocular bacterial infection.
Polymorphonuclear neutrophils (PMN) in Pseudomonas aeruginosa-infected cornea are required to clear bacteria from affected tissue, yet their persistence may contribute to irreversible tissue destruction. This study examined the role of C-X-C chemokines in PMN infiltration into P. aeruginosa-infected cornea and the contribution of these mediators to disease pathology. After P. aeruginosa challenge, corneal PMN number and macrophage inflammatory protein-2 (MIP-2) and KC levels were compared in mice that are susceptible (cornea perforates) or resistant (cornea heals) to P. aeruginosa infection. While corneal PMN myeloperoxidase activity (indicator of PMN number) was similar in both groups of mice at 1 and 3 days postinfection, by 5-7 days postinfection corneas of susceptible mice contained a significantly greater number of inflammatory cells. Corneal MIP-2, but not KC, levels correlated with persistence of PMN in the cornea of susceptible mice. To test the biological relevance of these data, resistant mice were treated systemically with rMIP-2. This treatment resulted in increased corneal PMN number and significantly exacerbated corneal disease. Conversely, administration of neutralizing MIP-2 pAb to susceptible mice reduced both PMN infiltration and corneal destruction. Collectively, these findings support an important role for MIP-2 in recruitment of PMN to P. aeruginosa-infected cornea. These data also strongly suggest that a timely down-regulation of the host inflammatory response is critical for resolution of infection.
Kernacki
K A
KA
Department of Anatomy, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Barrett
R P
RP
Hobden
J A
JA
Hazlett
L D
LD
D000818:Animals; D054426:Chemokine CXCL2; D015169:Colony Count, Microbial; D004198:Disease Susceptibility; D015818:Eye Infections, Bacterial / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D007106:Immune Sera / Q000008:administration & dosage; D007113:Immunity, Innate; D007274:Injections, Intraperitoneal; D007634:Keratitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007958:Leukocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015846:Monokines / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D020556:Neutrophil Infiltration / Q000276:immunology*; D011552:Pseudomonas Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000166:cytology / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage
D054426:Chemokine CXCL2; D007106:Immune Sera; D015846:Monokines; D012333:RNA, Messenger; D011994:Recombinant Proteins