Differential production of MCP-1 and cytokine-induced neutrophil chemoattractant in the ischemic brain after transient focal ischemia in rats.
Chemokines have been shown to play an important role in leukocyte infiltration into ischemic lesions. Recently, the increased expression of monocyte chemoattractant protein-1 (MCP-1) and cytokine-induced neutrophil chemoattractant (CINC) was observed in experimental stroke models where infiltrated leukocytes were supposed to induce tissue injury, however, the protein level and time course of these chemokines have not been fully elucidated. Therefore, we analyzed the time-dependent production of MCP-1 and CINC in the rat brain after transient middle cerebral artery occlusion (MCAO) by means of specific enzyme-linked immunosorbent assay systems. The MCP-1 levels in the ipsilateral hemispheres increased from 6 h, peaked at 2 days, and thereafter gradually decreased. The peak MCP-1 concentration was 89.2+/-28.2 ng/g tissue wet weight (mean +/- SEM, n = 5, 49.3-fold greater than the contralateral value at the same time, P < 0.05), which is supposed to be high enough to exert its biological effects. In contrast, the maximum CINC concentration that corresponded to 2.9+/-0.7 ng/g tissue wet weight (mean +/- SEM, n = 5, 55.0-fold greater than the contralateral value at the same time, P < 0.05), was observed at 6 h. In addition, we confirmed the temporal profile of leukocyte subtypes that infiltrated into the ischemic brain, thus, neutrophil infiltration occurred at early stages (1-3 days), followed by massive infiltration of macrophages at later stages (2-7 days). These studies suggest that MCP-1 in cerebral ischemia actually plays a significant role in the migration of macrophages into the lesion and that the differential temporal production of these chemokines contributes to the regulation of infiltrated leukocyte subtypes.
Yamagami
S
S
Teijin Institute for Bio-Medical Research, Tokyo, Japan. s.yamagami@teijin.co.jp
Tamura
M
M
Hayashi
M
M
Endo
N
N
Tanabe
H
H
Katsuura
Y
Y
Komoriya
K
K
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D019743:Chemokines, CXC / Q000378:metabolism; D002630:Chemotactic Factors / Q000096:biosynthesis*; D004195:Disease Models, Animal; D006133:Growth Substances / Q000096:biosynthesis*; D036341:Intercellular Signaling Peptides and Proteins; D002546:Ischemic Attack, Transient / Q000150:complications*; D007962:Leukocytes / Q000166:cytology; D008264:Macrophages / Q000166:cytology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D018932:Chemokine CCL2; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins