ライフサイエンスコーパス: properdin

1 highly active in the absence or presence of properdin.

2 pping epitopes on HS/heparin by factor H and properdin.

3 of 10 Neisserial strains tested bound native properdin.

4 at high (80%) serum concentrations required properdin.

5 AP and led to the consumption of C3, fB, and properdin.

6 cifically using native versus unfractionated properdin.

7 we demonstrate that the target of Salp20 is properdin.

8 pathway C3 convertase, and all reacted with properdin.

9 d endothelial labeling for C3, factor B, and properdin.

10 proteins CFHR1, C1q chains A, B, and C, and properdin.

11 eins 1, 2, 3, and 5, C1q chains B and C, and properdin.

12 nd C1q, whereas acLDL bound to C1q, IgM, and properdin.

13 ce; here, we show that these effects require properdin.

14 position on activated platelets with surface properdin.

15 lar HS, although to a different epitope than properdin.

16 ituting properdin-depleted serum with native properdin a priori enhanced C3 deposition on all strains

17 Additionally, properdin, a pivotal positive regulator of the alternati

18 Properdin, a plasma component that is also released by a

19 lbicin but is more active in the presence of properdin, a plasma protein that acts to stabilize C3bBb

20 We demonstrate that physiological properdin, a positive regulator of complement alternativ

21 study, we examined the impact of the lack of properdin, a positive regulator of complement, in C. rod

22 Properdin, a positive regulator of the alternative pathw

23 Recently, properdin, a positive regulator of the alternative pathw

24 scular injury, are among the main sources of properdin, a positive regulator of the alternative pathw

25 a common global fold that is very similar to properdin, a protein with six TSRs.

26 ed increased production of the antibacterial properdin, a regulator of the complement activation, as

27 to the effects of the alternative pathway is properdin, a serum glycoprotein that can both initiate a

28 Displacement of properdin accelerated the decay of the C3 convertase, le

29 We also determine that blockade of properdin activity prevents aneurysm formation.

30 ytometry was used to further explore whether properdin acts as an initial recognition molecule reacti

31 Properdin also promotes a large displacement of the TED

32 iscrimination between the initial binding of properdin and binding secondary to C3b deposition is a c

33 with complement components C1q, C3, C5, and properdin and blocking antibody-dependent cellular cytot

34 C3bBb complexes, because blocking decay with properdin and C3 nephritic factor did not restore C3bBb

35 Coincubation of properdin and factor H did not hamper HS/heparin binding

36 t in the mesangial immunodeposits, including properdin and factor H in the alternative pathway and ma

37 rt consensus repeat domains of CFHR5 contact properdin and mediate dimer formation.

38 urther, they demonstrate a critical role for properdin and support its therapeutic targeting in renal

39 Finally, we describe the interplay between properdin and the alternative pathway negative regulator

40 ng for PLA2R, IgG4, C3, C5b-9, factor B, and properdin and very weak staining for C1q, C4d, and IgG1.

41 ssue-specific knockout of Cfp (which encodes properdin) and by generating BM chimeric mice.

42 The impact from the development of FB, properdin, and C3 knockout mice closely follows this in

43 ernative pathway components factor B, C3 and properdin, and C3a receptor and C5a receptor were detect

44 unen precursor, histidine-rich glycoprotein, properdin, and complement C4-A isoform 1.

45 was described for TSRs of thrombospondin-1, properdin, and F-spondin within the sequence Cys-Xaa(1)-

46 had increased levels of AP factors B, H, and properdin, and fewer showed a "hyperinflammatory" subphe

47 a sequence motif shared with thrombospondin, properdin, and several complement proteins.

48 and C1q deposition, as well as C3, factor B, properdin, and terminal complement (C) components.

49 ve LN from inactive disease are ALCAM, PF-4, properdin, and VCAM-1 among African-Americans, sE-select

50 noglobulin (IgG-FH(1-5)) or to an anti-mouse properdin antibody (Anti-P-FH(1-5)).

51 components of the complement pathway, or of properdin, are susceptible to meningococcal disease.

52 These data implicate systemic properdin as a key contributor to AP complement-mediated

53 We therefore challenge the view of properdin as a pattern recognition molecule, and argue t

54 C3bBb, is well accepted, whereas the role of properdin as pattern recognition molecule is controversi

55 ion conformations of multiple TSR domains in properdin at medium resolution.

56 data show that physiological forms of human properdin bind directly to human platelets after activat

57 obra C3; this finding suggests that gC-1 and properdin bind to different sites on C3b.

58 the physiological P, P, and P forms of human properdin bind to the surface of Chlamydia pneumoniae di

59 on of alternative pathway-mediated lysis and properdin binding to C3b, but not of C5 binding to C3b,

60 in low anticoagulant heparinoids can inhibit properdin binding to tubular HS, with a minor effect on

61 vious work, by inhibiting C3, we showed that properdin binding to zymosan and Escherichia coli is not

62 Properdin binding was facilitated by the glycosaminoglyc

63 din-/- mouse serum correlated with the human properdin-binding affinity of the LPS.

64 t readily bound E. coli LPS mutants, and the properdin-binding capacity of each strain correlated wit

65 These properdin-binding segments are duplicated in two mutant

66 t of properdin on C3bBb would be attained as properdin binds more than one ligand at a time, forming

67 knowledge, that the human complement protein properdin binds to early apoptotic T cells and initiates

68 I also found that properdin binds to preformed alternative pathway C3 conv

69 Recently, we showed that properdin binds to tubular heparan sulfates (HS).

70 Here, we review basic properdin biology, emphasizing the major hurdles that ha

71 Factor H (fH) and properdin both modulate complement; however, fH inhibits

72 In contrast to properdin, both gCs bound to cobra C3; this finding sugg

73 ted in properdin-depleted serum this form of properdin bound efficiently to both substrates in a stri

74 These findings support a model in which properdin, bound to a target surface via C3b, iC3b, or o

75 plasmon resonance (SPR) surfaces coated with properdin, but SG7.AF binds with lower affinity than alb

76 eage cells as the principal source of plasma properdin by generating mice with global and tissue-spec

77 SA, normal human serum-induced deposition of properdin by zymosan was abolished by the C3-inhibiting

78 Alternatively, properdin can be recruited by C3(H2O) on the platelet su

79 Once bound to a surface, properdin can direct convertase formation and target upt

80 In this report, we demonstrate that properdin can directly bind to microbial targets and pro

81 mplicated the interpretation of results from properdin-centered studies.

82 e, we studied mice deficient in both CFH and properdin (CFH(-/-).P(-/-)).

83 tumor suppressive role of complement factor properdin (CFP) in vitro and in vivo.

84 Unfractionated properdin contains aggregates or high-order oligomers, i

85 Properdin could be represented by seven TSR domains, not

86 ly with apoptotic T cells, they suggest that properdin could play a similar role during apoptosis of

87 xposes binding sites for factors B, H and I, properdin, decay accelerating factor (DAF, CD55), membra

88 count for the effect of mutations that cause properdin deficiencies, and suggest that the biologicall

89 Properdin deficiency rescued mice from AP complement-med

90 Properdin-deficient mice and wild-type littermates compa

91 ed by sublethal cecal ligation and puncture, properdin-deficient mice appear immunocompromised, becau

92 We have generated a fully backcrossed properdin-deficient mouse line by conventional gene-spec

93 Properdin-deficient patients are susceptible to lethal m

94 nderstanding the selective predisposition of properdin-deficient patients to meningococcal infection.

95 In vitro, properdin-deficient serum is impaired in alternative pat

96 measured by factor B binding, occurred in a properdin-dependent manner.

97 The biological activity of properdin depends on the oligomerization state, but whet

98 ition than when bacteria were incubated with properdin-depleted serum alone.

99 Finally, properdin-depleted serum could not control Chlamydia pne

100 native properdin followed by the addition of properdin-depleted serum did not cause detectable increa

101 his assay, addition of purified properdin to properdin-depleted serum during convertase formation (st

102 re generated on rabbit erythrocytes by using properdin-depleted serum in the presence of C5 inhibitor

103 ver, after addition of native properdin, the properdin-depleted serum recovered the ability to contro

104 nated properdin, followed by the addition of properdin-depleted serum resulted in higher C3 depositio

105 to zymosan or E. coli, but when incubated in properdin-depleted serum this form of properdin bound ef

106 However, reconstituting properdin-depleted serum with native properdin a priori

107 pstatin on these substrates, indicating that properdin deposition depended on initial C3b deposition

108 Properdin did not bind wild-type Escherichia coli, but i

109 In solution, properdin dimers are curved molecules, whereas trimers a

110 Properdin-directed complement activation occurred on yea

111 The properdin-directed model is consistent with a proposal m

112 standard model and one that proceeds by the properdin-directed model.

113 In conclusion, the physiological forms of properdin do not bind directly to either N. meningitidis

114 We monitored properdin during AP activation and in complement-deficie

115 These outcomes position properdin early in the response to an infectious challen

116 Inhibition of endogenous properdin, either circulating in the blood or produced l

117 Cumulatively, our data indicate that properdin enhances PGA formation via increased productio

118 Properdin exists as either a dimer, trimer or tetramer.

119 Moreover, we found that properdin factor B, an alternative pathway complement ac

120 This review examines the new properdin findings and their implications.

121 isseriae, preincubating bacteria with native properdin followed by the addition of properdin-depleted

122 reincubation of bacteria with unfractionated properdin, followed by the addition of properdin-deplete

123 A rationale for such a means to supply properdin for immune reactions is proposed.

124 se gonococcal strains that bind C4BP require properdin for killing by 2C7, whereas strains that do no

125 All physiological properdin forms increase PGA formation, but properdin te

126 Properdin (FP) is an essential positive regulator of the

127 tors including C3, C4, factor B (fB), factor properdin (fP), mannose-binding lectin, C3aR, C5aR, or I

128 ent factor B protein that produces a stable, properdin-free AP C3 convertase, we show that properdin

129 Salp20 directly bound to and displaced properdin from the C3 convertase.

130 Previous reports suggest that properdin function depends on multiple interactions betw

131 ed production of C5a, and that inhibition of properdin function has therapeutic potential to limit th

132 The current understanding of properdin function is that it facilitates AP complement

133 osition on Neisseria decreased markedly when properdin function was blocked using an anti-properdin m

134 igomer structure is an integral component of properdin function.

135 e have localized about 6.5kb upstream of the properdin gene on the X chromosome.

136 t properdin localizes to mast cells and that properdin has the ability to directly associate with E.

137 um have complicated studies of its function, properdin has, regardless, emerged as a key player in va

138 factor H interaction and clearly differ from properdin-heparinoid interaction.

139 Principles governing properdin homeostasis are unknown.

140 us C3 activation via AP tickover to maintain properdin homeostasis.

141 pended on initial C3b deposition followed by properdin in a second step.

142 We therefore studied the role of properdin in activation of complement in normal human se

143 We examined the role of properdin in AP activation on diverse strains of Neisser

144 These results reveal a novel role of properdin in AP complement initiation and have implicati

145 e role of AP recruitment and, in particular, properdin in assisting killing of gonococci by specific

146 Here, we demonstrate a critical role for properdin in autologous tissue injury mediated by AP com

147 The role of properdin in complement activation on stimulated platele

148 y, these data point to an important role for properdin in facilitating immune Ab-mediated complement-

149 In the present study, we found that properdin in human serum bound dose-dependently to solid

150 New studies are now focusing on a role for properdin in inflammatory and autoimmune diseases.

151 Markedly reduced properdin in mice deficient in an AP component and its p

152 in normal renal tissues and colocalized with properdin in proteinuric kidneys.

153 Collectively, these data indicate that properdin in serum as well as polymorphonuclear-released

154 rnover in the maintenance of basal levels of properdin in the blood.

155 There was a >90% reduction of properdin in the Crry single-knockout mice (Crry SKO).

156 lomerular basement membrane, but the role of properdin in the pathophysiology is unknown.

157 tic T cells, whereas the binding activity of properdin in the serum appeared to be inhibited.

158 dition, we elaborate on an emerging role for properdin in thromboinflammation and discuss the potenti

159 Ab neutralization of properdin in WT mice similarly ameliorated arthritis dev

160 d at the level of initiating molecules (MBL, properdin) in the lectin/alternative pathways or C4b in

161 le of forming new convertases but containing properdin, in step 2 of the assay, again full C5b-9 form

162 a complement profile observed in humans with properdin-independent C3 nephritic factors.

163 ion of C3 driven by complete CFH deficiency, properdin influences the intraglomerular localization of

164 members of the CirpA family directly bind to properdin, inhibiting its ability to promote complement

165 tion was observed and blocked by addition of properdin inhibitor Salp20.

166 ctional and structural characterisation of a properdin inhibitor, opening avenues for future therapeu

167 mmation and discuss the potential utility of properdin inhibitors as long-term therapeutic options to

168 n preparations and the presence of potential properdin inhibitors in serum have complicated studies o

169 In conclusion, factor H and properdin interact with different HS epitopes of PTECs.

170 surface plasmon resonance assays to examine properdin interactions with C3b and factor B.

171 Properdin is a natural, positive regulator of the altern

172 Altogether, our data suggest that properdin is a pattern recognition molecule that plays a

173 Properdin is a plasma protein and is also released from

174 Properdin is a positive regulator of alternative pathway

175 Properdin is a positive regulator of AP complement activ

176 Properdin is a positive regulator of complement activati

177 Properdin is a positive regulator of complement activati

178 Recently, it has been shown that properdin is also a pattern-recognition molecule that bi

179 in C3-depleted human serum, or when purified properdin is applied in buffer.

180 Properdin is composed of multiple identical protein subu

181 ne targeting in the mouse, we show here that properdin is essential for AP complement activation indu

182 In this work, we showed that serum properdin is essential for LPS- and zymosan-induced C5b-

183 Thus, properdin is essential for the convertase specificity sw

184 e pathway on activated platelets occurs when properdin is on the surface and recruits C3b or C3(H2O)

185 Properdin is produced by many different leukocyte subset

186 roperdin-free AP C3 convertase, we show that properdin is required for the development of elastase-in

187 les act to control inappropriate activation, Properdin is the only known positive regulator of the hu

188 f the alternative pathway of complement, and properdin is the sole positive regulator.

189 serum as well as polymorphonuclear-released properdin is unable to bind and initiate direct alternat

190 Properdin is well known as an enhancer of the alternativ

191 Following infection, properdin knockout (P(KO)) mice had increased diarrhea a

192 lity of CFHR4-bound C3b to bind factor B and properdin, leading to an active convertase that generate

193 deposition in Cfh(-/-) mice and that plasma properdin levels are a sensitive marker of C5 convertase

194 Notably, the increases in plasma C5 and properdin levels persisted for longer than the increases

195 Notably, low properdin levels were significantly associated with the

196 C5 levels correlated with changes in plasma properdin levels.

197 n one ligand at a time, forming a lattice of properdin: ligand interactions bound to a surface scaffo

198 sidue peptide derived from the second type 1 properdin-like repeat of the antiangiogenic protein thro

199 tion involves CSVTCG sequences in the type 1 properdin-like repeats of TSP1, the known binding site f

200 th the thrombospondins 1 (TSP1) and 2 (TSP2) properdin-like type 1 repeats (TSR).

201 ivity of TSP-1 is mediated by the binding of properdin-like type I repeats to the receptor CD36.

202 We further show that properdin localizes to mast cells and that properdin has

203 Using a properdin loss of function mutation in mice and a mutant

204 properdin function was blocked using an anti-properdin mAb or when properdin was depleted from serum.

205 The role of the other TSR domains in properdin may be to act as spacers to make TSR-4, TSR-5

206 Here we studied whether properdin-mediated complement activation occurs on the s

207 n of C5a with its cellular receptor prevents properdin-mediated increases in PGA formation.

208 Our model explains how properdin mediates the assembly of stabilized C3/C5-conv

209 s abolished in properdin-/- mouse serum, and properdin-/- mice were unable to clear Crry-deficient er

210 were only partially or minimally affected in properdin-/- mice.

211 modules more exactly, we expressed the first properdin module (P1); the third properdin module (P3);

212 d the first properdin module (P1); the third properdin module (P3); the first and second properdin mo

213 gen module with the first, second, and third properdin modules (CP123) in the GELEX expression vector

214 properdin module (P3); the first and second properdin modules (P12); the first, second, and third pr

215 modules (P12); the first, second, and third properdin modules (P123); and the procollagen module wit

216 These results indicate that the properdin modules of TSP1 specifically interact with fib

217 Properdin monomers are pretzel-shaped molecules with lim

218 tore LPS-dependent AP complement activity in properdin-/- mouse serum correlated with the human prope

219 ed AP complement activation was abolished in properdin-/- mouse serum, and properdin-/- mice were una

220 e WES data sets, 1 mild hemophilia A case, 5 properdin mutated individuals, and 4 digenic complement

221 ritis development, whereas reconstitution of properdin-null mice with exogenous properdin restored ar

222 ron microscopy and solution scattering, that properdin oligomers adopt extended rigid and well-define

223 ds on the oligomerization state, but whether properdin oligomers are rigid and how their structure li

224 and C-terminal ends of adjacent monomers in properdin oligomers conform a curly vertex that holds to

225 complement exclusively via association with properdin on A. fumigatus as validated by detection of C

226 The full stabilizing effect of properdin on C3bBb would be attained as properdin binds

227 The role of properdin on microbes appears to be restricted to stabil

228 Finally, we demonstrate that the effects of properdin on PGA formation are tightly regulated by Fact

229 henotypic change to a differential effect of properdin on the dynamics of alternative pathway complem

230 a von Willebrand factor type C module, three properdin or thrombospondin type 1 repeat (TSR) modules,

231 nd the other is required for blocking C5 and properdin (P) binding to C3.

232 In this study, we investigated the role of properdin (P), a positive alternative pathway complement

233 We conclude properdin participates in two distinct complement activa

234 How properdin performs this function is, however, unclear.

235 We conclude that properdin plays a significant role in the outcome of pol

236 complement component, a recombinant form of properdin (Pn), with significantly higher activity than

237 e of nonphysiological aggregates in purified properdin preparations and experimental models that do n

238 of non-physiological aggregates in purified properdin preparations and the presence of potential pro

239 lement; however, fH inhibits activation, and properdin promotes activation of the alternative pathway

240 The regulator properdin promotes generation and stabilization of AP co

241 I demonstrated that properdin promotes the association of C3b with factor B

242 This enhanced surface binding and properdin recruitment was further evidenced in the mesan

243 Properdin regulates the alternative pathway of the compl

244 Finally, properdin released by activated neutrophils binds to act

245 Properdin released by activated neutrophils was particul

246 Properdin released from human polymorphonuclear cells st

247 n-2, MMP-12, MMP-9, Myeloperoxidase, PGRP-S, Properdin, Resistin, Serpin A4, and TIMP-1 are significa

248 tution of properdin-null mice with exogenous properdin restored arthritis sensitivity.

249 ward C5, and this function is independent of properdin's role in new convertase formation.

250 n this study, we sought to determine whether properdin serves as a focal point for the initiation of

251 Moreover, properdin:single-chain Ab constructs were used to direct

252 Two functions have been assigned to properdin; stabilization of the alternative convertase,

253 rum was not due in part to its effect on the properdin-stabilized C3 convertase, C3b,Bb,P.

254 On pathogen surfaces, properdin stabilizes C3/C5 convertases to efficiently fi

255 Properdin stabilizes convertases formed upon activation

256 Enhanced properdin staining correlated with local complement acti

257 he C3-convertase complex (C3bBb) formed on a properdin surface and inhibits the convertase activity o

258 "Properdin tagging" of apoptotic T cells also induced the

259 Moreover, the study suggests that properdin-targeting strategies may halt aneurysmal growt

260 ion to an equivalent extent, suggesting that properdin-targeting was not required for FH(1-5) to alte

261 properdin forms increase PGA formation, but properdin tetramers are the most efficient at increasing

262 Adding either properdin tetramers or C5a to whole blood increases CD11

263 maged human endothelial cell surfaces and to properdin, the human complement activator.

264 However, after addition of native properdin, the properdin-depleted serum recovered the ab

265 peptide also had no effect on the binding of properdin to C3, demonstrating that the observed inhibit

266 ut not gC-2, inhibited the binding of C5 and properdin to C3b and also inhibited the alternative path

267 at gC-1 sterically hindered access of C5 and properdin to C3b.

268 antigonococcal antiserum required functional properdin to kill C4BP-binding strains, but not C4BP-non

269 IgM, C1q, mannose-binding lectin (MBL), and properdin to LDL and acLDL were investigated by ELISA.

270 onse was reversed by administering exogenous properdin to P(KO) mice.

271 In this assay, addition of purified properdin to properdin-depleted serum during convertase

272 We further show that the ability of human properdin to restore LPS-dependent AP complement activit

273 Similarly, binding of properdin to the surface of human umbilical vein endothe

274 The complement protein properdin, traditionally viewed as a positive regulator

275 o surface-linked convertases is unlikely for properdin trimer and tetramers.

276 es have been assigned to the procollagen and properdin (Type I) modules of thrombospondin-1 (TSP1) ba

277 ertase activity was also fully restored when properdin was added together with C5b-9 components (step

278 However, and unexpectedly, properdin was also deficient in C3(-/-), fB(-/-), and fD

279 blocked using an anti-properdin mAb or when properdin was depleted from serum.

280 Within 10 min, properdin was partially restored in fB(-/-) but not in C

281 ently, commercially available unfractionated properdin was shown to bind to certain biological surfac

282 molecular structures of dimeric and trimeric properdin were studied by X-ray scattering and analytica

283 Properdin, which lacks the structural homology shared by

284 th significantly higher activity than native properdin, which promotes complement activation via the

285 ither genetic or pharmacological blockade of properdin, which we expected to be therapeutic, converte

286 c, and by blocking the interaction of C5 and properdin with C3b.

287 CFHR5, bound damaged human cell surfaces and properdin with greater intensity and exacerbated local c

288 uman kidney diseases, but whether inhibiting properdin would be beneficial in these diseases is unkno

289 3, suggesting that therapeutic inhibition of properdin would be detrimental in this setting.