Role for macrophage inflammatory protein-2 in lipopolysaccharide-induced lung injury in rats.
Macrophage inflammatory protein-2 (MIP-2) is a C-X-C chemokine that possesses chemotactic activity for neutrophils. Rat MIP-2 was cloned and expressed as a 7.9-kDa peptide that exhibited dose-dependent neutrophil chemotactic activity at concentrations from 10 to 250 nM. Rabbit polyclonal Ab to the 7.9-kDa peptide showed reactivity by western blot analysis and suppressed its in vitro chemotactic activity. Cross-desensitization chemotaxis experiments suggested that the chemotactic responses elicited by MIP-2 and the related chemokine, cytokine-induced neutrophil chemoattractant, may be mediated through a common receptor. Also, chemotactic responses to human GRO-alpha were blocked by exposure of human neutrophils to either GRO-alpha or rat MIP-2, suggesting conservation of this receptor-mediated response. After LPS instillation into rat lung, mRNA for MIP-2 was up-regulated in a time-dependent manner, peaking at 6 h. MIP-2 protein was detected in bronchoalveolar lavage fluids of these animals and a significant amount of chemotactic activity present in these fluids was attributed to MIP-2. On the basis of intrapulmonary instillation of Ab to MIP-2, neutrophil accumulation in lungs after airway instillation of LPS was found to be MIP-2-dependent. These data indicate that MIP-2 plays a significant role in LPS-induced inflammatory response in rat lungs and is required for the full recruitment of neutrophils.
Schmal
H
H
Department of Surgery, University Hospital, Zurich, Switzerland.
Shanley
T P
TP
Jones
M L
ML
Friedl
H P
HP
Ward
P A
PA
D000818:Animals; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002199:Capillary Permeability / Q000187:drug effects / Q000276:immunology; D054426:Chemokine CXCL2; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003001:Cloning, Molecular; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008969:Molecular Sequence Data; D015846:Monokines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects; D012333:RNA, Messenger / Q000302:isolation & purification; D051381:Rats; D011919:Rats, Inbred Strains
D054426:Chemokine CXCL2; D007106:Immune Sera; D008070:Lipopolysaccharides; D015846:Monokines; D012333:RNA, Messenger