Interaction of microglia and amyloid-beta through beta2-integrin is regulated by RhoA.
Amyloid-beta (Abeta) is one of the main factors to cause Alzheimer's disease. Although fibrillar Abeta (fAbeta) activates microglial cells that release toxic compounds to induce partial neuronal death, the mechanism of interaction between Abeta and microglia remains unclear. Therefore, we examined the interaction of microglial cells (BV2) and fAbeta on a gelatin-precoated plate. The binding was markedly enhanced by RhoA inactivation using Tat-C3, dominant negative RhoA, and si-RhoA. To identify the receptor for fAbeta, we tested various antibodies to mask receptors. Among them, anti-beta2-integrin antibody mostly suppressed cell binding to fAbeta. The incremental binding of cells induced by RhoA inhibition was also blocked by addition of anti-beta2-integrin antibody. These results suggest that RhoA inhibition stimulates beta2-integrin-mediated cell interaction to fAbeta.
Jeon
Yee-Jin
YJ
Department of Biochemistry, College of Medicine, Hallym University, Chuncheon, Kangwon-Do, Republic of Korea.
Won
Ha-Young
HY
Moon
Mi-Young
MY
Choi
Won-Ho
WH
Chang
Chun-Ho
CH
Lee
Jae-Yong
JY
Kim
Jaebong
J
Kim
Sung-Chan
SC
Kim
Yong-Sun
YS
Park
Jae-Bong
JB
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D018821:CD18 Antigens / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection / Q000379:methods; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D000906:Antibodies; D018821:CD18 Antigens; D010446:Peptide Fragments; D034741:RNA, Small Interfering; D020741:rho GTP-Binding Proteins