{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T13:50:38Z","timestamp":1767966638501,"version":"3.49.0"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2005,12,22]],"date-time":"2005-12-22T00:00:00Z","timestamp":1135209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2006,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Complement\u2010receptor\u20103 (CR3\/MAC\u20101), scavenger\u2010receptor\u2010AI\/II (SRAI\/II), and Fc\u03b3\u2010receptor (Fc\u03b3R) can mediate myelin phagocytosis in macrophages and microglia. Paradoxically, after injury to CNS axons these receptors are expressed but myelin is not phagocytosed, suggesting that phagocytosis is subject to regulation between efficient and inefficient states. In the present work, we focus on CR3\/MAC\u20101 and SRAI\/II\u2010mediated myelin phagocytosis. Phagocytosis by CR3\/MAC\u20101 and SRAI\/II was inhibited by cPKC inhibitor Go\u20106976, general\u2010PKC inhibitors Ro\u2010318220 and calphostin\u2010C, and BAPTA\/AM, which chelates intracellular Ca<jats:sup>2+<\/jats:sup> required for cPKC activation. Signaling\/activation by cPKC are thus suggested. PMA, which mimics diacylglycerol (DAG) as an activator of cPKC, novel\u2010PKC (nPKC), and non\u2010PKC DAG\u2010driven molecule(s), produced a dose\u2010dependent dual effect on phagocytosis by CR3\/MAC\u20101 and SRAI\/II, i.e., augmentation at low concentrations and inhibition at high concentrations. Inhibition of phagocytosis by CR3\/MAC\u20101 was enhanced by combining inhibiting concentrations of PMA with PKC inhibitors Go\u20106976 or Ro\u2010318220, suggesting inhibition by PMA\/DAG\u2010driven non\u2010PKC molecule(s). In contrast, inhibition of phagocytosis by SRAI\/II was enhanced by combining inhibiting concentrations of PMA with cPKC inhibitor Go\u20106976 but not with general\u2010PKC inhibitor Ro\u2010318220, suggesting inhibition by nPKC. Phagocytosis by CR3\/MAC\u20101 and SRAI\/II was further inhibited by PI3K inhibitors wortmannin and LY\u2010294002 and PLC\u03b3 inhibitor U\u201073122. Altogether, our observations suggest that CR3\/MAC\u20101 and SRAI\/II\u2010mediated myelin phagocytosis share activation by PI3K, PLC\u03b3 and cPKC. The two differ, however, in that non\u2010PKC DAG\u2010driven molecule(s) inhibit CR3\/MAC\u20101\u2010mediated phagocytosis, whereas nPKC inhibit SRAI\/II\u2010mediated phagocytosis. Each of these signaling steps may be targeted for regulating CR3\/MAC\u20101 and\/or SRAI\/II\u2010mediated phagocytosis between efficient and inefficient states. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.20304","type":"journal-article","created":{"date-parts":[[2005,12,22]],"date-time":"2005-12-22T17:17:56Z","timestamp":1135271876000},"page":"538-550","source":"Crossref","is-referenced-by-count":27,"title":["Non\u2010PKC DAG\/Phorbol\u2010Ester receptor(s) inhibit complement receptor\u20103 and nPKC inhibit scavenger receptor\u2010AI\/II\u2010mediated myelin phagocytosis but cPKC, PI3k, and PLC\u03b3 activate myelin phagocytosis by both"],"prefix":"10.1002","volume":"53","author":[{"given":"Goni","family":"Cohen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Makranz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maya","family":"Spira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuhiko","family":"Kodama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanny","family":"Reichert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shlomo","family":"Rotshenker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,12,22]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.17.1.593"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.8.4465"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.65.3.321"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01191555"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.151.7.1353"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3511"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20030727"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.296.5573.1655"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.3.1240"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.193.1.61"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.26.043002.094946"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3510095"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.2.414"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)45931-5"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1195"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.114.6.1039"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.64.2.228"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-1878(199905)21:5<422::AID-BIES9>3.0.CO;2-#"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.5.2809"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200205140"},{"key":"e_1_2_5_22_1","doi-asserted-by":"crossref","first-page":"778","DOI":"10.4049\/jimmunol.131.2.778","article-title":"Studies on demyelination in vitro: the requirement of membrane attack components of the complement system","volume":"131","author":"Liu WT","year":"1983","journal-title":"J Immunol"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2003.11.007"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M504861200"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)98335-3"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.1.458"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1999.00833.x"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr0002801"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(02)45041-0"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.4.496"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(96)00112-9"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1999.7229"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-9961(02)00008-6"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-05-03231.1994"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2001.0383"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.24.15045"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1385\/JMN:21:1:65"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.24.13158"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-3084(99)00013-4"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2000.7559"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.1123"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/386292a0"},{"key":"e_1_2_5_43_1","first-page":"5629","article-title":"Epidermal growth factor receptor\u2010stimulated activation of phospholipase Cgamma\u20101 promotes invasion of head and neck squamous cell carcinoma","volume":"63","author":"Thomas SM","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.10.3290"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1999.4701"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(05)00089-4"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2003.09.003"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fglia.20304","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.20304","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T03:46:57Z","timestamp":1695959217000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/glia.20304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,12,22]]},"references-count":46,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2006,4]]}},"alternative-id":["10.1002\/glia.20304"],"URL":"https:\/\/doi.org\/10.1002\/glia.20304","archive":["Portico"],"relation":{},"ISSN":["0894-1491","1098-1136"],"issn-type":[{"value":"0894-1491","type":"print"},{"value":"1098-1136","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,12,22]]}}}