Modulation of neutrophil influx in glomerulonephritis in the rat with anti-macrophage inflammatory protein-2 (MIP-2) antibody.

Abstract

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 Abinduced glomerular inflammation in the rat. (J. Clin. Invest.

NKT Cell Activation Mediates Neutrophil IFN-γ Production and Renal Ischemia-Reperfusion Injury

“…Chemokines mediate leukocyte migration into the injured kidney and IFN-␥ modulates chemokine production, including IFN-␥-inducing protein 10 (IP-10), monokine-induced by IFN-␥, and IFN-␥-inducible T cell chemoattractant production, which bind to CXCR3 to mediate T cell migration (25) (25)(26)(27)(28)(29)(30). Our previous study showed that renal IRI up-regulated IP-10 and MIP␣, MIP1␤, MIP2, which are thought to mediate T cell and neutrophil migration (31,32). The source of increased IFN-␥ production upon stimulation by IL-12 is mainly from Th1, NKT (14,33,34), and myeloid cells (35).…”

Mononuclear Cell-Infiltrate Inhibition by Blocking Macrophage-Derived Chemokine Results in Attenuation of Developing Crescentic Glomerulonephritis

“…MDC riboprobe was synthesized with incorporation of 35 S-UTP as previously described. 10 Following in situ hybridization and before dehydration, the slides were incubated for 5 minutes in Tris-buffered saline. Endogenous peroxidase, avidin, and biotin were inactivated, and then sections were incubated with mAb ED-1 or mAb CD8a and with peroxidaseconjugated goat anti-mouse IgG, followed by mouse PAP.…”

Monomeric Monocyte Chemoattractant Protein-1 (MCP-1) Binds and Activates the MCP-1 Receptor CCR2B

“…Based on the structure (33,34) and calculations of the difference in solvent accessibility between monomer and dimer, we identified several candidates for mutation including Tyr 13 , Thr 10 , Val 9 , and Pro 8 ( Fig. 1).…”

“…These residues form a short stretch of ␤-sheet at the interface between the two subunits. Tyr 13 and Tyr 13 Ј are oriented toward each other and in the crystal structure (34) are hydrogen bonded through an intervening water molecule. They also make hydrophobic contacts that stabilize the dimer by packing onto Val 9 of the opposing subunit.…”

“…Interest in these proteins was first stimulated by the observation of elevated levels in a number of inflammatory diseases (4,5) including rheumatoid arthritis (6,7), arteriosclerosis (8,9), and asthma (10). Although it is not clear whether excessive production is the cause or consequence of these diseases, the demonstration that neutralizing antibodies (11)(12)(13) reduced symptoms in a number of animal models generated optimism that receptor antagonists may have therapeutic benefit (14). Recently, it has been shown that certain chemokine receptors also serve as obligate coreceptors for entry of the human immunodeficiency virus into CD4ϩ cells (15)(16)(17) and that viral replication can be inhibited by the ligands of the coreceptors (18 -21).…”