ライフサイエンスコーパス: PF4

1 actions of the chemokine platelet factor 4 (PF4).

2 is further facilitated by platelet factor 4 (PF4).

3 s with positively charged platelet factor 4 (PF4).

4 ation step driven by PPIs between RANTES and PF4.

5 we found that activated T cells also express PF4.

6 f a symbiotic filamentous inoviral prophage, Pf4.

7 Finally, administration of PF4/44mer-DNA protein C aptamer complexes in mice induce

8 We showed that platelet factor 4 (PF4), a platelet-associated chemokine, binds and compact

9 plexed with surface-bound platelet factor 4 (PF4) activated by HIT antibodies contribute to the proth

10 the hypothesis that neoepitope formation on PF4 after binding to bacteria is an ancient host defense

11 PF4 also binds to bacteria, thereby exposing the same ne

12 leic acids, including aptamers, also bind to PF4 and enhance PF4 binding to platelets.

13 heparin in transgenic mice expressing human PF4 and FcgammaRIIA receptors.

14 KKO binding to PF4 and heparin is specifically inhibited by human HIT a

15 ining platelet factor 4 (PF4), antibodies to PF4 and heparin or cellular glycosaminoglycans (GAGs).

16 Beyond PF4 and HIT, the methods applied in the current study ma

17 defective secretion of the stored-chemokines PF4 and RANTES, but not newly synthesized IL-1beta, when

18 teins is lethal due to induction of prophage Pf4 and subsequent superinfection of the cell.

19 dies to complexes between platelet factor 4 (PF4) and heparin or cellular glycosaminoglycans.

20 ated by complexes between platelet factor 4 (PF4) and heparin or other polyanions, but the risk of th

21 ntibodies to complexes of platelet factor 4 (PF4) and heparin.

22 ts in the regulation of platelet activation (PF4) and systemic inflammation (tumor necrosis factor-al

23 es consisting of heparin, platelet factor 4 (PF4), and PF4/heparin-reactive Abs are central to the pa

24 es consisting of heparin, platelet factor 4 (PF4), and PF4/heparin-reactive antibodies are central to

25 proximately 10-fold faster on-rates than RTO-PF4, and apparent equilibrium dissociation constants dif

26 ine, platelet P-selectin, platelet factor 4 [PF4], and tumor necrosis factor-alpha).

27 feature that may explain why only some anti-PF4 antibodies are pathogenic.(1) In addition to epitope

28 Blood, Jaax and colleagues show that heparin-PF4 antibodies cross-reacted with nucleic acid (NA)-PF4

29 een model pathogenic and non-pathogenic anti-PF4 antibodies that might underlie their distinct pathop

30 Antiplatelet factor 4 (PF4) antibodies have an important role in the most frequ

31 mune complexes containing platelet factor 4 (PF4), antibodies to PF4 and heparin or cellular glycosam

32 heparin complexes require (1) an increase in PF4 antiparallel beta-sheets exceeding approximately 30%

33 ein C aptamer complexes in mice induced anti-PF4/aptamer antibodies, which cross-reacted with murine

34 ross-reacted with human PF4/nucleic acid and PF4/aptamer complexes, as shown by an enzyme immunoassay

35 near single-stranded DNA genome, and studied Pf4 assembly into liquid crystalline droplets using opti

36 Similar results are obtained for PF4 association with longer and structurally heterogeneo

37 in response to a rapid expansion of a lytic Pf4 bacteriophage, which may use type IV pili for infect

38 Understanding why the endogenous protein PF4 becomes immunogenic when complexing with heparin is

39 ed LPS structures show increasingly enhanced PF4 binding activity.

40 vely charged lipopolysaccharide (LPS) as the PF4 binding structure on Gram-negative bacteria.

41 In contrast, ODSH inhibited PF4 binding to gel-filtered platelets, displaced PF4 fro

42 abile plasma protein, fibronectin, inhibited PF4 binding to platelets in a dose-dependent fashion, pa

43 uding aptamers, also bind to PF4 and enhance PF4 binding to platelets.

44 g that phosphate residues of lipid A mediate PF4 binding.

45 To elucidate the intrinsic PF4-binding properties of HIT-like monoclonal antibody (

46 We now show that PF4 binds at multiple discrete sites along the surface o

47 d with chondroitin/dermatan sulfate and that PF4 binds to these GAG chains.

48 Additionally, platelet factor 4 (PF4) binds to bacteria and reduces the lag time for aggr

49 Strikingly, PF4 bound more efficiently to bisphosphorylated lipid A

50 PF4 bound strongest to mutants lacking the O-antigen and

51 KO, but not RTO, promoted oligomerization of PF4 but not PF4(K50E).

52 released by binding of >/=11-mer heparins to PF4, but not by smaller heparins.

53 uced platelet activation, suggesting that NA-PF4 can potentially cause a heparin-induced thrombocytop

54 ctor 4 (PF4), IgG antibodies against the Hep-PF4 complex, and platelet FcgammaRIIa.

55 ibodies cross-reacted with nucleic acid (NA)-PF4 complexes and induced platelet activation, suggestin

56 To mimic the effect of heparin in bringing PF4 complexes into proximity, we chemically cross-linked

57 ion experiments revealed that T cell-derived PF4 contributes to a restriction in Th17 differentiation

58 ram-negative bacteria and the amino acids of PF4 contributing to polyanion binding are highly conserv

59 Selectivity of Pf4-Cre and Cd11b-Cre mediated deletion was confirmed in

60 himeric mice reconstituted with Clec1b(fl/fl)PF4-Cre bone marrow, indicating that CLEC-2 expression i

61 We demonstrated that LNs of Clec1b(fl/fl)PF4-Cre mice are able to sustain primary immune response

62 ebral artery occlusion stroke Gna(i2)(fl/fl)/PF4-Cre mice developed significantly smaller brain infar

63 Dnm2(fl/fl) Pf4-Cre mice had severe macrothrombocytopenia with moder

64 ion under flow and a protection of Bin2fl/fl,Pf4-Cre mice in models of arterial thrombosis and stroke

65 gakaryocyte/platelet lineage in Clec1b(fl/fl)PF4-Cre mice led to the development of blood-filled LNs

66 ollowing myocardial ischemia, Gna(i2)(fl/fl)/PF4-Cre mice showed dramatically reduced reperfusion inj

67 in thrombopoiesis, we generated Dnm2(fl/fl) Pf4-Cre mice specifically lacking DNM2 in the megakaryoc

68 By crossing Gp1ba-Cre and Pf4-Cre mice to the mT/mG dual-fluorescence reporter mou

69 ammatory infarct progression, Gna(i2)(fl/fl)/PF4-Cre mice were subjected to experimental models of ce

70 megakaryocytes and platelets (Gna(i2)(fl/fl)/PF4-Cre mice) and found bleeding defects comparable to t

71 ice lacking PSMC1 in platelets (Psmc1(fl/fl) Pf4-Cre mice) exhibited severe thrombocytopenia and died

72 Deletion of platelet BIN2 (Bin2fl/fl,Pf4-Cre mice) resulted in reduced Ca2+ store release and

73 mice generated using either the Gp1ba-Cre or Pf4-Cre strains revealed similar platelet phenotypes.

74 This is partially a result of the Pf4-Cre transgene being expressed in a variety of leukoc

75 ader tissue expression was observed with the Pf4-Cre transgene, leading to recombination in many hema

76 The Syk(R41Afl/fl) mouse was crossed to a PF4-Cre(+) mouse to induce expression of the Syk mutant

77 However, chimera mice generated with Pf4-Cre(+)-Crry(flox/flox) bone marrows showed platelets

78 Rather than displaying thrombocytopenia, Pf4-Cre(+)-Crry(flox/flox) mice had normal platelet coun

79 on, suggesting that circulating platelets in Pf4-Cre(+)-Crry(flox/flox) mice were naturally selected

80 Examination of Pf4-Cre(+)-Crry(flox/flox) mouse bone marrows revealed e

81 Notably, Pf4-Cre(+)-Crry(flox/flox) mouse platelets became comple

82 s manner as shown by megakaryocyte-specific (Pf4-Cre) double-knockout mice.

83 Syk(R41Afl/fl;PF4-Cre) mice are born at approximately 50% of the expec

84 cy and have a similar phenotype to Syk(fl/fl;PF4-Cre) mice, including blood-lymphatic mixing and chyl

85 LEC-2 and GPVI is abolished in Syk(R41Afl/fl;PF4-Cre) platelets.

86 The Platelet factor 4-Cre recombinase (Pf4-Cre) transgenic mouse is the current model of choice

87 and immunological anomalies were observed in Pf4-Cre-generated KO mice as a result of nonspecific del

88 Pf4-Cre-mediated Jak2 deletion in PLTs and MKs did not c

89 tin (TPO) was maintained at normal levels in Pf4-Cre-positive Jak2(f/f) mice, consistent with reduced

90 e mice were crossed with mice transgenic for Pf4-Cre-recombinase (thrombopoietic deletion) or Cd11b-C

91 h Vps34 deletion in the MK/platelet lineage (Pf4-Cre/Vps34(lox/lox)).

92 platelet-derived chemokines RANTES/CCL5 and PF4/CXCL4 were lower in coinfection.

93 latelet-derived chemokine platelet factor 4 (PF4/CXCL4) stimulates VSMC injury responses both in vitr

94 with this antibody augmented the effects of PF4, decreasing NDP release and bacterial dissemination

95 PF4-deficient and platelet-deficient mice had exaggerate

96 We addressed this issue by characterizing PF4-dependent binding of HIT antibodies to intact platel

97 between the platelet activation assay and a PF4-dependent immunoassay for HIT antibodies indicates t

98 results raise the possibility that a unique Pf4-dependent, Mpl-independent progenitor cell is the ma

99 These longer polyanions can also induce PF4 dimer assembly when bound to the protein in relative

100 PF4 drives a VSMC inflammatory phenotype including a dec

101 We also demonstrate that PF4 effects are mediated, in part, through increased exp

102 itively charged chemokine platelet factor 4 (PF4) forms immunogenic complexes with heparin and other

103 binding to gel-filtered platelets, displaced PF4 from a PF4-transfected cell line, displaced PF4/hepa

104 MvaU results in an increase in expression of Pf4 genes and that cells that cannot produce type IV pil

105 o longer produce the replicative form of the Pf4 genome can tolerate the loss of both MvaT and MvaU.

106 se results provide a more nuanced picture of PF4-glycosaminoglycan interactions leading to complex fo

107 r HIT plasma samples led to cleavage of anti-PF4/H antibodies, which fully abolished the ability to i

108 hout any reduction in binding ability to the PF4/H complex.

109 In conclusion, cleavage of anti-PF4/H IgG by IdeS abolishes heparin-dependent cellular a

110 We evaluated whether cleavage of anti-PF4/H IgG by IdeS could suppress the pathogenicity of HI

111 Consistent with previous studies, anti-PF4/H IgG optical density transiently increased between

112 herefore, the transient kinetics of the anti-PF4/H IgG response resembled neither that of recall Abs

113 ved purified 5B9, a monoclonal chimeric anti-PF4/H IgG1, which led to the formation of single cleaved

114 f IgG Abs against platelet factor 4/heparin (PF4/H) complexes by day 6 after surgery.

115 A positive PF4/H-PaGIA result increased the probability of HIT in t

116 t) or intermediate 4Ts score plus a negative PF4/H-PaGIA result received prophylactic doses of danapa

117 A negative PF4/H-PaGIA result reduced the pretest probability of HI

118 ipants with a low 4Ts score (irrespective of PF4/H-PaGIA result) or intermediate 4Ts score plus a neg

119 ipants with a low 4Ts score (irrespective of PF4/H-PaGIA result) or intermediate 4Ts score plus negat

120 ult) or intermediate 4Ts score plus negative PF4/H-PaGIA result.

121 gel immunoassay (platelet factor 4/heparin [PF4/H]-PaGIA), and serotonin-release assay (SRA) perform

122 Additionally, PF4 had a higher affinity for endothelial-derived perlec

123 Although PF4 has been described as a platelet-specific molecule,

124 e complexes consisting of platelet factor 4 (PF4), heparin, and PF4/heparin-reactive antibodies are c

125 mmunoassays to detect antiplatelet factor 4 (PF4)/heparin antibodies is hindered by detection of anti

126 munoassays detecting anti-platelet factor 4 (PF4)/heparin antibodies, derived a diagnostic algorithm

127 platelet-activating anti-platelet factor 4 (PF4)/heparin antibodies.

128 lop autoantibodies to the platelet factor 4 (PF4)/heparin complex, which is termed the HIT Ab complex

129 Antibodies specific for platelet factor 4 (PF4)/heparin complexes are the hallmark of heparin-induc

130 r caused by antibodies to platelet factor 4 (PF4)/heparin complexes.

131 magnitude of the antiplatelet factor 4 (anti-PF4)/heparin immune response (by serotonin-release assay

132 trongly positive for anti-platelet factor 4 (PF4)/heparin immunoglobulin (Ig)G in 2 different immunoa

133 onoclonal antibody KKO to platelet factor 4 (PF4)/heparin.

134 wever, only a fraction of patients with anti-PF4-heparin antibodies develop HIT, implying that only a

135 e basis for the pathogenic potential of anti-PF4-heparin antibodies remains unclear.

136 re obtained for KKO and RTO interacting with PF4-heparin complexes.

137 wn about the specific molecular mechanism of PF4-heparin interactions.

138 s from platelet surfaces, and inhibited anti-PF4/heparin Ab binding to PF4/heparin complexes and subs

139 any effect on the interaction of PF4 or anti-PF4/heparin Abs with platelets.

140 Here, we show that anti-PF4/heparin antibodies are readily generated in wild-typ

141 Moreover, heparin-induced anti-human-PF4/heparin antibodies cross-reacted with human PF4/nucl

142 It is now recognized that anti-PF4/heparin antibodies develop commonly after heparin ex

143 ese data indicate that the formation of anti-PF4/heparin antibodies in postoperative patients may be

144 first- and second-line immunoassays for anti-PF4/heparin antibodies is accurate for ruling in or out

145 breakdown of B-cell tolerance produced anti-PF4/heparin antibodies spontaneously.

146 To bind anti-PF4/heparin antibodies, PF4/heparin complexes require (1

147 to distinguish properties of pathogenic anti-PF4/heparin antibodies, we compared isotype-matched mono

148 ents with suspected HIT and circulating anti-PF4/heparin antibodies.

149 bited PF4/heparin binding to platelets, anti-PF4/heparin antibody binding to PF4/heparin complexes, a

150 e mechanism that incites such prevalent anti-PF4/heparin antibody production in more than 50% of pati

151 y binding to PF4/heparin complexes, and anti-PF4/heparin antibody-induced platelet activation as a re

152 with PF4/heparin complex formation and anti-PF4/heparin antibody-induced platelet activation.

153 erfering with PF4/heparin complexes and anti-PF4/heparin antibody-platelet interaction, thus explaini

154 Pathogenic antibodies to PF4/heparin bind and activate cellular FcgammaRIIA on pl

155 Fibronectin also inhibited PF4/heparin binding to platelets, anti-PF4/heparin antib

156 vivo, we used a murine mAb specific for the PF4/heparin complex (KKO), as well as plasma from patien

157 into B-cell-deficient muMT mice responded to PF4/heparin complex challenge by producing PF4/heparin-s

158 into B-cell-deficient muMT mice responded to PF4/heparin complex challenge.

159 sed PF4/heparin-specific IgG production upon PF4/heparin complex challenge.

160 y-induced platelet activation as a result of PF4/heparin complex disruption.

161 ngs suggest that fibronectin interferes with PF4/heparin complex formation and anti-PF4/heparin antib

162 ic Abs in Foxp3-deficient mice and inhibited PF4/heparin complex-induced production of PF4/heparin-sp

163 to identify a plasma factor interfering with PF4/heparin complexes and anti-PF4/heparin antibody-plat

164 and inhibited anti-PF4/heparin Ab binding to PF4/heparin complexes and subsequent platelet activation

165 of PF4 to B cells is heparin dependent, and PF4/heparin complexes are found on circulating B cells f

166 In healthy donors, PF4/heparin complexes bind preferentially to B cells (>9

167 from a PF4-transfected cell line, displaced PF4/heparin complexes from platelet surfaces, and inhibi

168 To bind anti-PF4/heparin antibodies, PF4/heparin complexes require (1) an increase in PF4 ant

169 Binding of PF4/heparin complexes to B cells is mediated through the

170 posure, we first examined the interaction of PF4/heparin complexes with cells circulating in whole bl

171 aHIT prevention strategy through disrupting PF4/heparin complexes with low-sulfated heparin; the for

172 telets, anti-PF4/heparin antibody binding to PF4/heparin complexes, and anti-PF4/heparin antibody-ind

173 enerated in wild-type mice on challenge with PF4/heparin complexes, and that antibody production is s

174 ODSH prevents formation of immunogenic PF4/heparin complexes, and, when given together with hep

175 Complement is activated by PF4/heparin complexes, co-localizes with antigen on B ce

176 dies to demonstrate complement activation by PF4/heparin complexes, opsonization of PF4/heparin to B

177 antibodies, which cross-reacted with murine PF4/heparin complexes.

178 hanistic insights into the immunogenicity of PF4/heparin complexes.

179 lyspecific and immunoglobulin (Ig)G-specific PF4/heparin enzyme-linked immunosorbent assays (ELISAs)

180 out proximate heparin exposure and with anti-PF4/heparin IgG antibodies that cause strong in vitro pl

181 Anti-PF4/heparin IgG became detectable at day 7 (median), ie,

182 compared reactivities in the SRA and an anti-PF4/heparin IgG-specific enzyme immunoassay (EIA), testi

183 To investigate a modulating risk for PF4/heparin immunization and breakthrough of HIT, we als

184 tin levels could represent a risk factor for PF4/heparin immunization and clinical breakthrough of HI

185 ary considerably with respect to the risk of PF4/heparin immunization and, among antibody-positive pa

186 opments have clarified mechanisms underlying PF4/heparin immunogenicity, disease susceptibility, and

187 entially to B cells (>90% of B cells bind to PF4/heparin in vitro) relative to neutrophils, monocytes

188 y low numbers, lending support to a model of PF4/heparin interaction in which the latter wraps around

189 on by PF4/heparin complexes, opsonization of PF4/heparin to B cells via CD21, and the presence of com

190 ven the high proportion of B cells that bind PF4/heparin, we investigated complement as a mechanism f

191 o increased cell activation by antibodies to PF4/heparin, with a lower inhibitory effect of endogenou

192 ing of heparin, platelet factor 4 (PF4), and PF4/heparin-reactive Abs are central to the pathogenesis

193 ing of heparin, platelet factor 4 (PF4), and PF4/heparin-reactive antibodies are central to the patho

194 ing of platelet factor 4 (PF4), heparin, and PF4/heparin-reactive antibodies are central to the patho

195 une responses, but their role in controlling PF4/heparin-specific Ab production is unknown.

196 cells play an important role in suppressing PF4/heparin-specific Ab production.

197 eg cells prevented spontaneous production of PF4/heparin-specific Abs in Foxp3-deficient mice and inh

198 ice, Rag1-deficient recipients also produced PF4/heparin-specific Abs spontaneously.

199 functional Treg cells spontaneously produced PF4/heparin-specific Abs.

200 IL-10-deficient mice spontaneously produced PF4/heparin-specific Abs.

201 s from unmanipulated wild-type mice produced PF4/heparin-specific antibodies following in vitro or in

202 ipheral blood of healthy adults that produce PF4/heparin-specific antibodies following in vitro stimu

203 o PF4/heparin complex challenge by producing PF4/heparin-specific antibodies of IgG2b and IgG3 isotyp

204 PF4/heparin-specific antibodies produced by wild-type mi

205 herefore, breakdown of tolerance can lead to PF4/heparin-specific antibody production, and B-cell tol

206 demonstrate that MZ B cells are critical for PF4/heparin-specific antibody production.

207 d mice possess preexisting inactive/tolerant PF4/heparin-specific B cells.

208 suggest that breakdown of tolerance leads to PF4/heparin-specific B-cell activation and antibody prod

209 Short-term IL-10 administration suppresses PF4/heparin-specific IgG production in wild-type mice.

210 T cell-specific deletion of IL-10 increased PF4/heparin-specific IgG production upon PF4/heparin com

211 ed PF4/heparin complex-induced production of PF4/heparin-specific IgGs in wild-type mice.

212 y developed humanized monoclonal antibody to PF4/heparin.

213 ore >/=4 points; positive platelet factor 4 [PF4]/heparin immunoassay, positive serotonin-release ass

214 we report the synthesis of a covalent RANTES-PF4 heterodimer (termed OPRAH) by total chemical synthes

215 ific to platelet factor 4/heparin complexes (PF4/Hs) that activate platelets via FcgammaRIIA.

216 ontrol groups, with or without antibodies to PF4/Hs.

217 e risk of HIT in patients with antibodies to PF4/Hs.

218 omponents--heparin (Hep), platelet factor 4 (PF4), IgG antibodies against the Hep-PF4 complex, and pl

219 t that although all HIT antibodies recognize PF4 in a complex with heparin, only a subset of these an

220 Absence of PF4 in the host leads to exaggerated Th17 differentiatio

221 important mechanistic role for platelets and PF4 in VSMC injury responses both in vitro and in vivo.

222 nd 4 (CXCL4, also named platelet factor 4 or PF4) in the bone marrow, and we found that CXCL4 regulat

223 We now show that PF4 increases NET-mediated bacterial capture, reduces th

224 is of the force histograms revealed that KKO-PF4 interactions had approximately 10-fold faster on-rat

225 uses native mass spectrometry to investigate PF4 interactions with relatively short heparin chains (u

226 ed additional insight into the ways in which PF4 interacts with components of the vasculature to modu

227 taining IgG antibodies to platelet factor 4 (PF4) involved in heparin-induced thrombocytopenia (HIT),

228 , the results of this study demonstrate that PF4 is a key regulator of Th cell development that is ne

229 egative, bind to and activate platelets when PF4 is present without any requirement for heparin (P <

230 PF4 is stored in platelet alpha-granules bound to the gl

231 discovered that chemokine platelet factor 4 (PF4) is a negative regulator of Th17 differentiation.

232 Platelet factor 4 (PF4) is produced by platelets with roles in both inflamm

233 imilar binding probabilities to cross-linked PF4(K50E), which forms few if any oligomers.

234 RTO, promoted oligomerization of PF4 but not PF4(K50E).

235 se total binding or binding to nontetrameric PF4(K50E).

236 In contrast to WT PF4, KKO and RTO showed lower and similar binding probab

237 Pf4-Lox(tg/tg) mice had a normal number of platelets; ho

238 othelial injury was significantly shorter in Pf4-Lox(tg/tg) mice, indicating a higher propensity for

239 ploring underlying mechanisms, we found that Pf4-Lox(tg/tg) platelets adhere better to collagen and h

240 However, the higher affinity of Pf4-Lox(tg/tg) platelets to the collagen sequence GFOGER

241 X in wild-type megakaryocytes and platelets (Pf4-Lox(tg/tg)) were generated.

242 ed by secreted filamentous molecules such as Pf4 may be a general strategy of bacterial survival in h

243 ed in the aorta (91.6%) and heart (99.2%) of Pf4 mice, but there was no change in expression in eithe

244 ecreased by 85% and absent in platelets from Pf4 mice.

245 G) antibodies, which bind platelet factor 4 (PF4) modified by polyanions, such as heparin (H).

246 PF4 monomer/RTO-Fab complex (a non-HIT anti-PF4 monoclonal antibody).

247 murine monoclonal HIT-like antibody) and (3) PF4 monomer/RTO-Fab complex (a non-HIT anti-PF4 monoclon

248 Binding of RTO to PF4 monomers prevents PF4 tetramerization and inhibits K

249 A monoclonal antibody KKO which binds to PF4-NET complexes, further enhances DNase resistance.

250 /heparin antibodies cross-reacted with human PF4/nucleic acid and PF4/aptamer complexes, as shown by

251 n postoperative patients may be augmented by PF4/nucleic acid complexes.

252 e receptor genes (CX3CR1, CX3CL1, CXCR3, and PF4) on systemic inflammation and platelet activation se

253 roxaban had any effect on the interaction of PF4 or anti-PF4/heparin Abs with platelets.

254 t-HIA-IgG, HemosIL-AcuStar-HIT-IgG, and ID-H/PF4-PaGIA in retrospective (n = 221) and prospective (n

255 In 121 (17.6%) of 687 unresolved cases, ID-H/PF4-PaGIA was used as second-line testing (additional TA

256 emosIL-AcuStar-HIT-IgG) and titer >=16 (ID-H/PF4-PaGIA); cutoffs with 100% NPV were <0.13 U/mL and <=

257 beyond exposure to heparin implicating other PF4 partners.

258 ated because it results in the production of Pf4 phage that superinfect and kill cells or inhibit the

259 a parental strain that cannot be infected by Pf4 phage to define the collective MvaT and MvaU regulon

260 e type IV pili are resistant to infection by Pf4 phage.

261 ic aptamers has the potential to induce anti-PF4/polyanion antibodies and a prothrombotic diathesis.

262 IgG/PF4/polyanion complexes directly activate platelets via

263 caused by immunoglobulin G directed against PF4/polyanion complexes.

264 Thus, formation of stable PF4 polymers results in much stronger interactions with

265 The Pf4 population diversified with an evolutionary rate of

266 , 1.16-1.56) and one downstream of the genes PF4/PPBP/CXCL5 (rs1595009, P = 1.3 x 10(-4); OR, 1.32; 9

267 se driven by the megakaryocyte (MK)-specific Pf4 promoter permits the conditional knockout of Itga2 i

268 the control of the mouse platelet factor 4 (Pf4) promoter generated megakaryocytes with markedly red

269 factors (CD26, FGF, HGF, MMP-8, MMP-9, OPN, PF4, SDF-1) and cytokines (IL-1ra, IL-16) in BM Soup.

270 and that release of secondary mediators and PF4 serve as a positive feedback mechanism for activatio

271 ondaparinux binds to the 'closed' end of the PF4 tetramer and stabilizes its conformation.

272 we solve the crystal structures of the: (1) PF4 tetramer/fondaparinux complex, (2) PF4 tetramer/KKO-

273 : (1) PF4 tetramer/fondaparinux complex, (2) PF4 tetramer/KKO-Fab complex (a murine monoclonal HIT-li

274 Binding of RTO to PF4 monomers prevents PF4 tetramerization and inhibits KKO and human HIT IgG-i

275 peutic approach: pharmacologic disruption of PF4 tetramers essential for formation of immune complexe

276 s into proximity, we chemically cross-linked PF4 tetramers using glutaraldehyde.

277 spectroscopy to induce structural changes in PF4 that resemble those induced by heparin.

278 PF4-TLR4(-/-) mice demonstrated significant protection f

279 -) platelets from either global TLR4(-/-) or PF4-TLR4(-/-) mice were functional but failed to respond

280 elet-specific TLR4(-/-) mice were generated (PF4-TLR4(-/-) mice).

281 Binding of PF4 to B cells is heparin dependent, and PF4/heparin com

282 The binding of PF4 to perlecan was found to inhibit both FGF2 signaling

283 surface-attached antibodies with oligomeric PF4 to simulate interactions on cells.

284 binding of the chemokine platelet factor 4 (PF4) to polyanions induces heparin-induced thrombocytope

285 gel-filtered platelets, displaced PF4 from a PF4-transfected cell line, displaced PF4/heparin complex

286 The chemokine platelet factor 4 (PF4) undergoes conformational changes when complexing wi

287 morphisms explained 0.98% and 1.23% of serum PF4 variance in African Americans and whites, respective

288 Our study highlights the importance of PF4 variants in the regulation of platelet activation (P

289 d Spi-1, Gata2, and Gfi1b and reduced Zfpm1, Pf4, Vwf, and Mpl expression.

290 Disruption of PF4-VWF complex formation may provide a new therapeutic

291 ody KKO and HIT patient antibodies recognize PF4-VWF complexes, promoting platelet adhesion and enlar

292 Disruption of PF4-VWF-HIT antibody complexes by drugs that prevent or

293 Platelet adhesion to the PF4-VWF-HIT antibody complexes is inhibited by antibodie

294 es recognize more subtle epitopes induced in PF4 when it binds to CS, the major platelet glycosaminog

295 Third, Pf4, which had been considered specific for platelets an

296 nucleic acids augment complex formation with PF4, while single nucleotides or single-stranded polyA o

297 electron cryomicroscopy atomic structures of Pf4 with and without its linear single-stranded DNA geno

298 orimetry we characterized the interaction of PF4 with unfractionated heparin (UFH), its 16-, 8-, and

299 Association of platelet factor 4 (PF4) with heparin is a first step in formation of aggreg

300 arin increased the avidity of KKO binding to PF4 without affecting RTO, but it did not increase total