Modulation of neutrophil influx in glomerulonephritis in the rat with anti-macrophage inflammatory protein-2 (MIP-2) antibody.
The role of the chemokine, macrophage inflammatory protein-2 (MIP-2), during anti-glomerular basement membrane (GBM) antibody (Ab) glomerulonephritis (GN) was studied. Rat MIP-2 cDNA had been cloned previously. Recombinant rat MIP-2 (rMIP-2) from Escherichia coli exhibited neutrophil chemotactic activity and produced neutrophil influx when injected into the rat bladder wall. By using a riboprobe derived from the cDNA and an anti-rMIP-2 polyclonal Ab, MIP-2 was found to be induced in glomeruli with anti-GBM Ab GN as mRNA by 30 min and protein by 4 h, with both disappearing by 24 h. The expression of MIP-2 correlated with glomerular neutrophil influx. A single dose of the anti-MIP-2 Ab 30 min before anti-GBM Ab was effective in reducing neutrophil influx (40% at 4 h, P < 0.01) and periodic acid-Schiff deposits containing fibrin (54% at 24 h, P < 0.01). The anti-rMIP-2 Ab had no effect on anti-GBM Ab binding (paired-label isotope study). Functional improvement in the glomerular damage was evidenced by a reduction of abnormal proteinuria (P < 0.05). These results suggest that MIP-2 is a major neutrophil chemoattractant contributing to influx of neutrophils in Ab-induced glomerular inflammation in the rat.
Feng
L
L
Department of Immunology, Scripps Research Institute, La Jolla, California 92037.
Xia
Y
Y
Yoshimura
T
T
Wilson
C B
CB
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001483:Base Sequence; D054426:Chemokine CXCL2; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D003001:Cloning, Molecular; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000235:genetics; D005786:Gene Expression Regulation; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D017403:In Situ Hybridization; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007375:Interleukin-1 / Q000032:analysis; D007678:Kidney Glomerulus / Q000473:pathology*; D008168:Lung / Q000473:pathology; D008969:Molecular Sequence Data; D015846:Monokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology*; D051381:Rats; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D001743:Urinary Bladder / Q000473:pathology
D054426:Chemokine CXCL2; D016207:Cytokines; D007375:Interleukin-1; D015846:Monokines; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1