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To investigate the relationship between drusen and AMD, we focused on amyloid \u03b2 (A\u03b2), a major component of drusen and also of senile plaques in the brain of Alzheimer's patients. We previously reported that A\u03b2 was accumulated in drusen\u2010like structure in senescent neprilysin gene\u2010disrupted mice. The purpose of this study was to investigate the influence of A\u03b2 on factor B, the main activator of the complement alternative pathway. The results showed that A\u03b2 did not directly modulate factor B expression in RPE cells, but increased the production of monocyte chemoattractant protein\u20101 (MCP\u20101). A\u03b2 also increased the production of IL\u20101\u03b2 and TNF\u2010\u03b1 in macrophages\/microglia, and exposure of RPE cells to IL\u20101\u03b2 and TNF\u2010\u03b1 significantly up\u2010regulated factor B. Co\u2010cultures of RPE cells and macrophages\/microglia in the presence of A\u03b2 significantly increased the expression of factor B in RPE. These findings indicate that cytokines produced by macrophages\/microglia that were recruited by MCP\u20101 produced in RPE cells stimulated by A\u03b2 up\u2010regulate factor B in RPE cells. Thus, a combined mechanism exists for A\u03b2\u2010induced for the activation of the complement alternative pathway in the subretinal space; cytokine\u2010induced up\u2010regulation of activator factor B and dysfunction of the inhibitor factor I by direct binding to A\u03b2 as suggested in our earlier study. J. Cell. Physiol. 220: 119\u2013128, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.21742","type":"journal-article","created":{"date-parts":[[2009,4,22]],"date-time":"2009-04-22T03:21:01Z","timestamp":1240370461000},"page":"119-128","source":"Crossref","is-referenced-by-count":89,"title":["Amyloid\u2010\u03b2 up\u2010regulates complement factor B in retinal pigment epithelial cells through cytokines released from recruited macrophages\/microglia: Another mechanism of complement activation in age\u2010related macular degeneration"],"prefix":"10.1002","volume":"220","author":[{"given":"Jiying","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoko","family":"Ohno\u2010Matsui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriaki","family":"Shimada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizuko","family":"Ichinose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuji","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Mochizuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuo","family":"Morita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,3,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm950"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2003.10.011"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(96)30684-2"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/10454411950060020301"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0047-6374(01)00311-6"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.1.491"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.3.1872"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0169-328X(93)90097-9"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006982-198808020-00005"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1993.1158"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31692"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1110189"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401753"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2004.06.011"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0161-5890(96)84610-4"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1750"},{"key":"e_1_2_6_18_1","first-page":"81","volume-title":"Age\u2010related 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