ライフサイエンスコーパス: C5b-9

1 3/7) and lung deposition of collagen and C' (C5b-9).

2 he cytolytic membrane attack complex (MAC or C5b-9).

3 significantly more lytic activity than with C5b-9.

4 minal complement activation products C5a and C5b-9.

5 deposition of C4 and C3 and the formation of C5b-9.

6 r LY294002 reversed the protective effect of C5b-9.

7 did not affect C5b-7 uptake or hemolysis by C5b-9.

8 godendrocytes was significantly increased by C5b-9.

9 is of oligodendrocytes was also inhibited by C5b-9.

10 ace and are abnormally sensitive to lysis by C5b-9.

11 blocks in vitro generation of C3a, C5a, and C5b-9.

12 for deposition of C3 fragments and activated C5b-9.

13 f the potent proinflammatory factors C5a and C5b-9.

14 illaries but only a few of these reacted for C5b-9.

15 as generation of the membrane attack complex C5b-9.

16 ntly increased serum levels of C3a, C5a, and C5b-9.

17 ore formation by the membrane attack complex C5b-9.

18 gG3kappa deposits together with C3, C1q, and C5b-9.

19 netic properties differed for C9 addition to C5b-9(1) (0.27 s(-1) at 25 degrees C, 21 kcal/mol), indi

20 2 and 15 times that of C9 for the C5b-8 and C5b-9(1) complexes, respectively.

21 Assembly of monomeric FITC-C9 with C5b-8 or C5b-9(1) produced a substantial decrease in fluorescence

22 Clusterin binding to C5b-8 and C5b-9(1) was reversible with affinities that were 2 and

23 ase of RBC-derived microvesicles coated with C5b-9, a process that was inhibited by EDTA, in the abse

24 C5b-9 activates Akt as shown by in vitro kinase assay an

25 This indication of physiologic levels of C5b-9 activation in normal kidney potentially explains t

26 n was mediated by both surface-bound C3b and C5b-9 activity.

27 However, C5b-9 alone did not initiate proliferation or commenceme

28 d the terminal complement complex neoantigen C5b-9 along the outer surface of the Schwann cells.

29 capillary deposition of C1q, C3, C4d, and/or C5b-9 along with immunoglobulin, including IgG, with var

30 C5b-9 also down-regulated the expression of FasL and the

31 Complement C5b-9 also induced parallel activation of GEF-H1 and Rho

32 infected patients displayed a lower level of C5b-9 and a reduced antimicrobial effect on model organi

33 Clusterin inhibited C9 assembly on C5b-8 and C5b-9 and also bound to C5b-7 to prevent membrane attach

34 rine C3d was better than C3, plasma C4d, Bb, C5b-9 and anti-double-stranded DNA antibody in distingui

35 Deposition of iC3b and C5b-9 and bacterial killing occurred when bacteria were

36 Immunofluorescence showed that C5b-9 and C4d deposition occurred linearly along the epi

37 C5b-9 and C4d were almost universally deposited linearly

38 Both C5b-9 and C5b-7, but not C5b6, increased Raf-1 kinase ac

39 as accommodated grafts had low deposition of C5b-9 and high expression of CD59.

40 ro after injury that was induced by sublytic C5b-9 and PA.

41 correlated with staining for complement (C3, C5b-9) and IgG1 isotype in glomerular immune deposits.

42 MAC is composed of C5b to C9 (C5b-9) and mediates cell lysis of invaded pathogens.

43 s (C3a and C5a) and membrane attack complex (C5b-9) and opsonizes targeted cells.

44 5aR, local and systemic induction of soluble C5b-9, and amplified expression of C3aR/C5aR in lesions.

45 nce showed no significant reduction in C3 or C5b-9, and electron microscopy revealed persistent depos

46 ns were analyzed for deposition of C1q, C4d, C5b-9, and immunoglobulin (IgG, IgM, and IgA).

47 tion of exogenous antigen, mouse IgG, C3 and C5b-9, and podocyte injury.

48 nase and Akt activities were also induced by C5b-9, and the phosphatidylinositol 3-phosphate kinase i

49 position of the complement components C4 and C5b-9, and this correlated with an increase in bacterici

50 C3 and C5b-9 are found in immune deposits of IMN kidney biopsy

51 The effects of C5b-9 are mediated via signaling pathways, including cal

52 We show that the terminal complement complex C5b-9 assembles rapidly on the basal surface of cultured

53 onents through its ATPase domain and inhibit C5b-9 assembly and stability.

54 mbrane C5b-9 assembly, and the prevention of C5b-9 assembly on endothelial cells via upregulation of

55 t protect self cells from C3b deposition and C5b-9 assembly on their surfaces.

56 The impact on C5b-9 assembly was the most potent.

57 stream of C3a and C5a receptors and membrane C5b-9 assembly, and the prevention of C5b-9 assembly on

58 ERK1 activity was 2-fold increased by C5b-9 at 2 min and by C5b-7 at 10 min, over the C5b6 lev

59 onstrated co-localization of Cav-1-EGFP with C5b-9 at the plasma membrane, in early endosomes, at the

60 n exposed to sublytic (<5% lysis) amounts of C5b-9, become activated.

61 tor expression and for IgG, IgM, C3, C4, and C5b-9 binding after incubation in 100% human serum.

62 miR-200b/c overexpression reduced C5b-9 binding and enhanced its release from the cells an

63 e evaluated for the presence of C4d, Bb, and C5b-9 by quantitative microassay plate enzyme immunoassa

64 Preventing the endocytosis of C5b-9 by RPE cells led to structural defects in mitochon

65 rface and that processing and destruction of C5b-9 by this route are essential for RPE cell survival.

66 sy specimen showed granular staining for C3, C5b-9, C1q, and IgG3kappa; electron microscopy revealed

67 ease activity at subsequent visits than were C5b-9, C3, and C4.

68 ase activity at all 3 visits than were serum C5b-9, C3, and C4.

69 ed for complement activation products (ELISA-C5b-9, C4d, activated C1, and C5a) and major complement-

70 Levels of C5b-9, C4d, and activated C1 were significantly increase

71 Tissue sections were stained for C5b-9, C4d, and laminin.

72 EC, a major downstream target of PI3K, or if C5b-9 can induce the migration of AEC, a critical step i

73 were treated with ICs together with nonlytic C5b-9, changes associated with T cell activation by poss

74 In support of this idea, we observed that C5b-9 colocalizes with the early endosome marker EEA1 an

75 gs demonstrated increased immunostaining for C5b-9 compared with nontransplanted controls, confirming

76 Activation of complement and assembly of the C5b-9 complement complex have been implicated in the pre

77 plement-derived peptides and of the terminal C5b-9 complement components that comprise the membrane a

78 d for vascular deposits of IgG, IgM, and the C5b-9 complement membrane attack complex.

79 olytic proteolytically activated form of C5 (C5b)-9 complex.

80 Soluble C5b-9 complex concentrations in zymosan-activated human

81 The C5b-9 complex is the executioner of CDC.

82 s, Factor X, and complement proteins (C5 and C5b-9 complex) were identified in all drusen phenotypes.

83 Sections were immunostained with anti-human C5b-9 complex, the terminal complement cascade (TCC) neo

84 generation of the anaphylotoxin C3a and the C5b-9 complex.

85 avage of C5, and production of the cytolytic C5b-9 complex.

86 n of the anaphylatoxin C5a and the cytolytic C5b-9 complex.

87 sly shown by us to bind to components of the C5b-9 complex.

88 CDC, probably by facilitating purging of the C5b-9 complexes by endocytosis and exo-vesiculation.

89 Thus, cells actively remove the C5b-9 complexes from their plasma membrane by endocytosi

90 We have previously shown that sublytic C5b-9 complexes, through posttranslational regulation of

91 C5b-9 components of complement were present diffusely in

92 hich stain for IgG, C3, and membrane attack (C5b-9) components of complement and (2) the excretion of

93 Zymosan profoundly elevated soluble C5b-9 concentrations in human sera in vitro.

94 L-10, and complement membrane attack complex C5b-9 concentrations using enzyme-linked immunoassay.

95 C5b-9-dependent adhesion was blocked by neuraminidase tr

96 <0.0003) and the amount of C1q, C3, C4d, and C5b-9 deposition (P <0.05).

97 ivation shows an inverse correlation between C5b-9 deposition and the level of mortalin in the cell.

98 of the transplanted lung revealed decreased C5b-9 deposition compared with controls.

99 cal staining confirmed a reduction in C3 and C5b-9 deposition in Crry-transfected cells.

100 hemolysis and inhibited both C3 fragment and C5b-9 deposition on ADP-activated HMEC-1 cells, an exper

101 rong C1q and C3b, but relatively low C4b and C5b-9 deposition on analyzed cell lines.

102 rs of the hybrid CFHR1/CFH gene induced more C5b-9 deposition on endothelial cells than control serum

103 Decreased C3bi and C5b-9 deposition on RBCs and neutrophils was documented

104 ith local complement activation with C3b and C5b-9 deposition on the mesangial cell surface in vitro

105 occurred despite a significant reduction in C5b-9 deposition per lesion unit area, suggesting the cr

106 Increased C5b-9 deposition was evident by confocal microscopy and

107 Activated C5b-9 deposition was seen adjacent to tumor nests in a m

108 C3 and C5b-9 deposition were demonstrated in the renal cortex o

109 0% human plasma induced complement C3b/c and C5b-9 deposition, cellular activation and coagulation ac

110 Damaged glomeruli showed IgM, IgG, C4d, and C5b-9 deposition.

111 n the graft were responsible for the lack of C5b-9 deposition.

112 Cs) and neutrophils were stained to evaluate C5b-9 deposition.

113 irment of complement regulation, measured as C5b-9 deposition.

114 n (IgM and IgG) and complement (C3, C4d, and C5b-9) deposition, as well as with subsequent increases

115 In this study, we show glomerular C5b-9 deposits in the renal biopsy of a child with EHEC-

116 culizumab, whereas serum-induced endothelial C5b-9 deposits normalized after treatment, paralleled or

117 Using assays of ex vivo serum-induced C3 and C5b-9 deposits on endothelial cells, we documented that

118 ot serum from remission, caused wider C3 and C5b-9 deposits than control serum on unstimulated human

119 lomerulonephritis, serum-induced endothelial C5b-9 deposits were normal.

120 C5b-9 deposits were present in 78.6% of TMA cases and in

121 mutation carriers, induced excessive C3 and C5b-9 deposits.

122 dy, we assessed the formation and release of C5b-9 during early reperfusion in clinical kidney transp

123 ese data suggest that sublytic deposition of C5b-9 during hyperacute rejection results in the express

124 significantly inhibited formation of C3a and C5b-9 during SECC.

125 These C5b-9 effects were reversed by PI3K inhibitor LY294002.

126 Cells protect themselves from CDC by C5b-9 elimination, a process involving the mitochondrial

127 lasmid or by treatment with Dynasore reduced C5b-9 endocytosis and enhanced CDC.

128 a dominant negative plasmid had no effect on C5b-9 endocytosis and on cell death.

129 C5b-9 endocytosis was also disrupted by pretreatment of

130 lasmid sensitized cells to CDC and inhibited C5b-9 endocytosis.

131 C5b-9 endothelial deposits might help monitor eculizumab

132 iR-200 (b and c), suggesting that complement C5b-9 exerts a feedback-regulatory effect on these miRNA

133 of Cav-1 and cholesterol depletion abrogated C5b-9 exo-vesiculation, whereas, over-expression of Cav-

134 whereas, over-expression of Cav-1 increased C5b-9 exo-vesiculation.

135 N with intense staining for PLA2R, IgG4, C3, C5b-9, factor B, and properdin and very weak staining fo

136 t activation as measured by soluble terminal C5b-9 formation and C3c deposition on the CC surface.

137 This was demonstrated in vitro by C5b-9 formation and C5a active fragment production in th

138 nteractions, aVn-induced inhibition of lytic C5b-9 formation and of serum killing could be reversed.

139 he tubulointerstitium and that prevention of C5b-9 formation in tubules could slow the deterioration

140 These findings suggest that C5b-9 formation resulting from proteinuria contributes t

141 sulting in decreased C4b, iC3b, and terminal C5b-9 formation.

142 eases in C3b deposition, C3a generation, and C5b-9 formation.

143 Membrane attack complex (C5b-9) formation and Gram's staining revealed that compl

144 The C5b-9 forms lytic or non lytic pores in the cell membran

145 When cells were exposed to C5b-9, GTP-bound Ras in anti-C5b-9 immunoprecipitates wa

146 were exposed to C5b-9, GTP-bound Ras in anti-C5b-9 immunoprecipitates was increased 3.2-fold at 2 min

147 ctivation, as evidenced by the generation of C5b-9 immunoreactive terminal complement complexes in as

148 sed IL-1b, CCL2, and CFB as well as enhanced C5b-9 immunostaining were observed by confocal microscop

149 not reflected by renal tissue deposition of C5b-9 in biopsies taken 45 min after reperfusion.

150 To elucidate the role of C5b-9 in complement-mediated effects on renal tubular ce

151 esults not only confirm the critical role of C5b-9 in complement-mediated hemolysis and but also high

152 ts in all cases, suggesting a long t(1/2) of C5b-9 in extracellular matrix.

153 Normal renal biopsies stained positive for C5b-9 in glomeruli, tubular basement membranes, and vess

154 and but also highlight the critical role of C5b-9 in inflammasome activation.

155 We first assembled the C5b-9 in situ on the membrane and observed its assembly

156 , with CD59 functioning by binding C5b-8 and C5b-9 in the assembling complex.

157 C9(-/-)) for directly dissecting the role of C5b-9 in the pathogenesis of human diseases.

158 eye, as evidenced by increased deposition of C5b-9 in the retinal pigment epithelium (RPE) and choroi

159 Fas pathway in OLG apoptosis and the role of C5b-9 in this process.

160 ular deposition of IgG (mostly IgG4, C3, and C5b-9) in a granular pattern typical of MN.

161 ntiplasmin [PAP]), and complement (C3b, C5a, C5b-9) in baboons infused with factor Xa (FXa) and phosp

162 on and sublytic terminal complement complex (C5b-9) in CD4(+) T-cell responses is not investigated.

163 e of the complement membrane attack complex (C5b-9) in mediating hyperacute rejection has been demons

164 deposition of membrane attack complex (MAC, C5b-9) in nerve membranes.

165 which blocks the formation of human C5a and C5b-9, in preventing the immune-mediated motor neuropath

166 time an important role for C6, and therefore C5b-9, in the pathogenesis of nonimmunologic tubulointer

167 Sublytic C5b-9 increased extracellular signal-regulated kinase-1

168 activation are potential mechanisms by which C5b-9 increases survival of oligodendrocyte in vitro and

169 r the activation products iC3b, C4d, Bb, and C5b-9 indicated that ABri and ADan are able to fully act

170 Exposure to C5b-9 induced an inhibition of caspase-8 activation, Bid

171 Furthermore, ICs and nonlytic C5b-9 induced T cell proliferation and IFN-gamma product

172 C5b-9-induced cell cycle activation was inhibited by pre

173 ts that the PI3K/Akt pathway is required for C5b-9-induced cell cycle activation.

174 -specific inhibitor PD 098,059 abolished the C5b-9-induced DNA synthesis.

175 A major finding was that sublytic C5b-9-induced injury caused an increase in DNA damage in

176 ugmented the DNA damage response to sublytic C5b-9-induced injury.

177 passive Heymann nephritis (PHN)), complement C5b-9-induced proteinuria was associated with the activa

178 In this study, we show that C5b-9 induces AEC proliferation and migration and also a

179 These results show that sublytic C5b-9 induces DNA damage in vitro and in vivo and may ex

180 We have shown that C5b-9 induces proliferation and activates phosphatidylin

181 lytic activation of complement, particularly C5b-9, induces cell cycle progression in aortic smooth m

182 erimental membranous nephropathy, complement C5b-9-induces glomerular epithelial cell (GEC) injury an

183 C5b-9 inhibited the mitochondrial pathway of apoptosis i

184 sisting of C5b, C6, C7, C8, and C9 proteins (C5b-9) inhibits caspase-3 activation and apoptotic death

185 Here we induced sublytic C5b-9 injury in vitro by exposing cultured rat podocytes

186 a subset of Abeta42 plaques and, along with C5b-9 IR, was localized to dystrophic neurites in a subs

187 increase in DNA synthesis, however, sublytic C5b-9 is associated with a delay in G(2)/M phase progres

188 ffector products, cleaved C3, cleaved C5, or C5b-9, is responsible.

189 lial cell (GEC) injury induced by complement C5b-9 leads to proteinuria.

190 C3 level in 22/50 (43%) and elevated soluble C5b-9 level in 27/34 (79%) patients.

191 tistical significance (p = .090) and soluble C5b-9 levels were significant only for dose (p = .023).

192 C5b-9 levels were significantly increased in NP tissue c

193 ases in soluble terminal complement complex (C5b-9) levels after challenge with lethal Stx1 (n = 6) o

194 luble terminal complement complex formation (C5b-9) locally and active TGF-beta1 systemically.

195 easurements of complement biomarkers C5a and C5b-9 may confirm the diagnosis of aHUS and differentiat

196 data indicate that cell cycle activation by C5b-9 may involve p34CDC2 activity through RGC-32.

197 ediated injury, while CD59 limits consequent C5b-9-mediated cell damage.

198 deposits initiate complement activation and C5b-9-mediated damage of the overlying podocyte.

199 Thus, GEC CYP2B1 contributes to complement C5b-9-mediated injury and plays an important role in the

200 n, was significantly decreased by complement C5b-9-mediated injury but was preserved in CYP2B1-silenc

201 lternative complement pathway activation and C5b-9-mediated tubular injury can occur in MN and other

202 d glycoprotein CD59 inhibits assembly of the C5b-9 membrane attack complex (MAC) of human complement.

203 s as the principle cellular inhibitor of the C5b-9 membrane attack complex (MAC) of human complement.

204 bits the activity of the C9 component of the C5b-9 membrane attack complex (MAC), thereby protecting

205 suggesting that complement activation to the C5b-9 membrane attack complex had a casual role in renal

206 At a sublytic dose, the C5b-9 membrane attack complex protects oligodendrocytes

207 Quantification of the binding of the C5b-9 membrane attack complex to cells during complement

208 and mediate formation of the proinflammatory C5b-9 membrane attack complex, in functionally active fo

209 nd attenuated deposition of C3 fragments and C5b-9 membrane attack complexes on cell surfaces.

210 IR for C4d and C5b-9 (membrane attack complex, MAC) was observed in sma

211 IgG-kappa in the same distribution as C3 and C5b-9, mimicking monoclonal Ig deposition disease (MIDD)

212 se the possibility that ICs and the nonlytic C5b-9 modulate T cell-mediated responses in systemic lup

213 Samples were assayed for C3a and C5b-9, monocyte activation (CD11b upregulation), PMN act

214 of the terminal complement products C5a and C5b-9 occur only on the VWF-A2 domain.

215 he formation of the membrane attack complex (C5b-9 of complement).

216 bly of the terminal membrane attack complex (C5b-9) of complement.

217 C5b-9 often colocalized with von Willebrand factor in lu

218 igodendrocytes, and the inhibitory effect of C5b-9 on apoptotic process were investigated.

219 e lysis and deposition of complement C3b and C5b-9 on endothelial cells and platelets, we now show th

220 complement complexes (TCC) C5b-7, C5b-8, and C5b-9 on target cells during acute and chronic inflammat

221 cytic pathway to prevent the accumulation of C5b-9 on the cell surface and that processing and destru

222 ade in human plasma and caused deposition of C5b-9 on the platelet surface.

223 in oligodendrocyte apoptosis and the role of C5b-9 on this process.

224 he cytolytic membrane attack complex (MAC or C5b-9) on host cell membranes.

225 ization of C9 to the C5b-8 complex forms the C5b-9 (or MAC).

226 0001) as was the degree of C1q, C3, C4d, and C5b-9 ( P<0.05).

227 contrast, significantly lower deposition of C5b-9 (P < 0.0001), fibrin (P = 0.009), and diminished e

228 These studies demonstrate that C5b-9 plays an important role in hyperacute rejection of

229 n of terminal complement components (C5a and C5b-9) prevents platelet and neutrophil (PMN) but not mo

230 lement-dependent cytotoxicity (CDC) with its C5b-9 protein complex that is assembled on cell surfaces

231 ne of 50 dermatomyositis specimens contained C5b-9 reactive endomysial microvessels but none of these

232 Reduction in glomerular C3d and C9/C5b-9 reactivity was observed after daily administration

233 and cell activation properties, both C5a and C5b-9 regulate the downstream inflammatory cascade, whic

234 Our data indicate that C5b-9 regulation of the cell cycle activation in AEC thr

235 Further investigation of the process of C5b-9 removal by exo-vesiculation demonstrated that inhi

236 Assembly of sublytic C5b-9 resulted in inhibition of caspase-3 activation.

237 There was no release of soluble C5b-9 (sC5b-9) from living donor kidneys, nor was there

238 C4d and C5b-9 should be investigated as possible diagnostic biom

239 myopathologic findings are active myopathy, C5b-9 staining of endomysium, focal perivascular and per

240 inhibit complement activation at the C3 and C5b-9 step, respectively.

241 sphorylated at Ser-256 and inactivated after C5b-9 stimulation as shown by a decrease in DNA binding

242 Deposition of complement components C3 and C5b-9 (the membrane attack complex), however, was reduce

243 indicating activation of complement (C4d and C5b-9), the complement inhibitor apolipoprotein J (apo J

244 previously shown that generation of sublytic C5b-9, the membrane attack complex of complement, induce

245 In this study, we observed deposition of C5b-9, the terminal product of complement activation, in

246 wing the insertion of sublytic quantities of C5b-9, there is an increase in signaling pathways and gr

247 These data suggest that C5b-9 through PI3K signaling can rescue OLG from Fas-med

248 rocyte apoptosis is, therefore, inhibited by C5b-9 through post-translational regulation of Bad.

249 presence of the dynamin inhibitor dynasore, C5b-9 was almost completely retained at the cell surface

250 ozen section, human IgG and IgM, C3, C4, and C5b-9 was deposited on islets with increased intensity i

251 osition of complement components C3, C6, and C5b-9 was enhanced on the surface of the CspA mutant com

252 ted in the diabetic retinas, suggesting that C5b-9 was generated via the alternative pathway, the spo

253 ing of C1q to RGC and accumulation of C3 and C5b-9 was investigated using immunohistochemical and pro

254 by C3d deposition but deposition of C5b and C5b-9 was limited.

255 Moreover, C5b-9 was present in >75% of the TMA samples, suggesting

256 tivation [C3a, C5a, and terminal C' complex (C5b-9)] was attenuated in il17a(-/-) mice, and IL-17A ne

257 inal complement complex, also referred to as C5b-9, we incubated these immune reactants with peripher

258 f C4d, mannose-binding lectin, C1q, IgM, and C5b-9 were scored in the glomeruli, peritubular capillar

259 and terminal complement activation (C5a and C5b-9) were increased in the plasma of these 19 patients

260 d grafts had deposition of IgM, IgG, C3, and C5b-9 with low expression of CD59, whereas accommodated