Differential expression of macrophage inflammatory protein-2 and monocyte chemoattractant protein-1 in experimental glomerulonephritis.
We examined the relation between glomerular expression of chemokines from alpha-subfamily (macrophage inflammatory protein-2, MIP-2) and beta-subfamily (monocyte chemoattractant protein-1, MCP-1) and infiltration of neutrophils and monocytes in antibody mediated glomerulonephritis in rats. In the accelerated model of nephrotoxic nephritis (NTN), glomerular expression of MIP-2 and MCP-1 genes correlated with the sequential migration of neutrophil and monocyte influx, respectively. These relationships were investigated further in the heterologous phase of NTN by applying various treatments known to modulate the severity of injury. Pretreatment with bacterial lipopolysaccharide resulted in greater injury, MIP-2 expression increased 25- to 50-fold, and the glomerular neutrophil count increased two- to fourfold. Both MIP-2 mRNA levels and neutrophil infiltration were reduced by additional pretreatment with IL-6, IL-1 receptor antagonist, soluble IL-1 receptor or soluble TNF receptor (Spearman correlation coefficient r = 0.897, P < 0.005). In the heterologous phase of NTN, different pre-treatments only resulted in trivial changes in MCP-1 expression and monocyte infiltration. In conclusion, glomerular MIP-2 gene expression correlates with neutrophil infiltration both temporally during the evolution of nephritis, and when glomerular injury is modified by treatment. Glomerular MCP-1 gene expression correlates with monocyte influx. The data show chemokines of alpha- and beta-subfamilies co-operative to cause selective and sequential migration of different leukocyte subsets during development of antibody mediated glomerulonephritis.
Tam
F W
FW
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, England, United Kingdom.
Karkar
A M
AM
Smith
J
J
Yoshimura
T
T
Steinkasserer
A
A
Kurrle
R
R
Langner
K
K
Rees
A J
AJ
D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D054426:Chemokine CXCL2; D015870:Gene Expression; D005921:Glomerulonephritis / Q000209:etiology / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D015846:Monokines / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D015846:Monokines; D012333:RNA, Messenger