Neutrophil infiltration as a crucial step for monocyte chemoattractant protein (MCP)-1 to attract monocytes in lipopolysaccharide-induced arthritis in rabbits.
OBJECTIVE
To evaluate the mechanism whereby monocyte chemoattractant protein (MCP)-1 attracts monocytes in vivo.


METHODS
New Zealand white rabbits (175 rabbits) were used.


METHODS
LPS, MCP-1 or IL-8 was injected into knee joints. Antibodies against various cytokines or IL-1 receptor antagonist were injected to neutralize cytokine activities.


METHODS
The numbers of leukocyte populations, levels of cytokines in joints were estimated.


RESULTS
Partial inhibition of neutrophil influx with anti-IL-8 IgG (10 microg) suppressed LPS-induced macrophage influx by 43 +/- 8.5% (p<0.05) without affecting the MCP-1 level. Intraarticular injection of MCP-1 (1-30 microg) induced macrophage influx. The event was accompanied by a small number of neutrophils in an early phase. Co-injection of IL-8 (1.0 microg) enhanced the MCP-1-induced macrophage infiltration (p < 0.01). In neutrophil-depleted rabbits, LPS failed to induce macrophage influx even though the MCP-1 level was maintained, and macrophage influx following exogenously administered MCP-1 was also dramatically inhibited.


CONCLUSIONS
Early events associated with neutrophil infiltration appear to be important for MCP-1 to induce a later macrophage influx in LPS-arthritis.
Miyazaki
S
S
Department of Pathology, Kumamoto University School of Medicine, Japan.
Matsukawa
A
A
Ohkawara
S
S
Takagi
K
K
Yoshinaga
M
M
D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000473:pathology*; D018932:Chemokine CCL2 / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology; D004731:Endotoxins; D007596:Joints / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000187:drug effects*; D020556:Neutrophil Infiltration / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D011135:Polysaccharides, Bacterial; D011817:Rabbits
D018932:Chemokine CCL2; D016207:Cytokines; D004731:Endotoxins; D011135:Polysaccharides, Bacterial; C044101:endotoxin, Escherichia coli