ライフサイエンスコーパス: PF4

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

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

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

4 contain insertions in genes of the prophage Pf4.

5 ation step driven by PPIs between RANTES and PF4.

6 n/thrombomodulin (IIa/TM) in the presence of PF4.

7 to des-Arg(9)-BK by TAFIa in the presence of PF4.

8 inhibition of megakaryocyte colony growth by PF4.

9 we found that activated T cells also express PF4.

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

11 Platelet factor 4 (PF4), a platelet alpha-granule protein and a soluble cof

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

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

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

15 PF4 and CD163 gene expression within human atherosclerot

16 assays but retained high affinity binding to PF4 and effectively reversed PF4 binding to immobilized

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

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

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

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

21 own to mediate endothelial cell responses to PF4 and so we tested this receptor's importance in PF4's

22 ELISA that correlate with oligomerization of PF4 and sustained high-avidity interactions that may sim

23 ovide evidence that complexes formed between PF4 and TM's CS may play a physiologic role in potentiat

24 ltimolecular complexes of platelet factor 4 (PF4) and heparin (H).

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

26 cognize complexes between platelet factor 4 (PF4) and heparin or glycosaminoglycan side chains.

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

28 r caused by antibodies to platelet factor 4 (PF4) and heparin.

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

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

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

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

33 ion at micromolar concentrations, designated PF4 antagonists (PF4As).

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

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

36 e hundred fifteen patients with anti-heparin/PF4 antibodies detected by enzyme-linked immunosorbent a

37 eveals differences in the properties of anti-PF4 antibodies that cause thrombocytopenia not revealed

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

39 dent sample of 97 patients with anti-heparin/PF4 antibodies.

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

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

42 We observed that although PF4 or anti-PF4 antibody alone did not alter neutrophil function, co

43 latelet factor 4 (PF4/CXCL4) binding to anti-PF4 antibody can stimulate neutrophil activation, simila

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

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

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

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

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

49 ed LPS structures show increasingly enhanced PF4 binding activity.

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

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

52 nity binding to PF4 and effectively reversed PF4 binding to immobilized TM.

53 PF4 binding to neutrophils was blocked by chondroitinase

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

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

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

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

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

59 Strikingly, PF4 bound more efficiently to bisphosphorylated lipid A

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

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

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

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

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

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

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

67 antibodies to the heparin/platelet factor 4 (PF4) complexes via enzyme-linked immunosorbent assay.

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

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

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

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

72 FlnA(loxP) PF4-Cre bone marrows and spleens have a 2.5- to 5-fold i

73 ncreases blood platelet counts in FlnA(loxP) PF4-Cre mice and reveals the desintegration of FlnA-null

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

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

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

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

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

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

80 FlnA(loxP) PF4-Cre mice that lack FlnA in the megakaryocyte (MK) li

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

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

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

84 Srf in megakaryocyte development, we crossed Pf4-Cre mice, which express Cre recombinase in cells com

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

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

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

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

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

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

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

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

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

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

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

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

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

98 Pf4-Cre/Srf(F/F) knockout (KO) mice are born with normal

99 PF4-Cre/survivin(fl/fl) mice harbored normal platelet co

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

101 centration of PF4 suggest similarity between PF4/CS complexes and those that bind HIT antibodies.

102 omplexes formed following platelet factor 4 (PF4/CXCL4) binding to anti-PF4 antibody can stimulate ne

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

104 our different ELR-devoid CXC chemokines (ie, PF4/CXCL4, IP-10/CXCL10, MIG/CXCL9, and IP-9/CXCL11), we

105 PF4-deficient and platelet-deficient mice had exaggerate

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

107 ese complexes by HIT antibodies reverses the PF4-dependent enhancement in aPC generation and may cont

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

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

110 r ability to retain high affinity binding to PF4 despite having greatly diminished anticoagulant acti

111 sistance to the superinfective bacteriophage Pf4, detected only in biofilms.

112 ac-1 up-regulation peaked at an intermediate PF4 dose, suggesting that functional response varies wit

113 PF4 drives a VSMC inflammatory phenotype including a dec

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

115 On the basis of data from the heparin/PF4 enzyme-linked immunosorbent assay and confirmatory a

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

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

118 Deletion of the PF4 gene that encodes CXCL4 reduces atherosclerotic lesi

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

120 aT and MvaU are to repress the expression of Pf4 genes.

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

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

123 Although the early onset of the anti-PF4/H IgG response is compatible with a secondary immune

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

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

126 ies indicate that PRT/H and lysozyme/H, like PF4/H, show H-dependent binding over a range of H concen

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

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

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

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

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

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

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

134 We have previously shown that PF4:H multimolecular complexes assemble through electros

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

150 eparin complexes and the interaction of anti-PF4/heparin Abs with platelets.

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

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

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

154 ther causes, and development of asymptomatic PF4/heparin antibodies in patients treated with heparin.

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

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

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

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

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

160 complexes as shown by binding of human anti-PF4/heparin antibodies.

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

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

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

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

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

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

167 parin with minimal anticoagulant effects) on PF4/heparin complexes and the interaction of anti-PF4/he

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

169 , induce epitopes on PF4 resembling those on PF4/heparin complexes as shown by binding of human anti-

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

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

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

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

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

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

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

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

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

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

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

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

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

183 This can induce anti-PF4/heparin IgG Abs.

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

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

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

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

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

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 antibodies are central to the patho

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

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

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

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

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

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

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

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

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

202 y developed humanized monoclonal antibody to PF4/heparin.

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

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

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

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

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

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

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

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

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

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

213 equences of inhibition of TAFI activation by PF4 included loss of TM-dependent prolongation of clot l

214 Moreover, prophage Pf4 integrated into the chromosome of Pseudomonas aerugi

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

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

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

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

219 rast to stimulation of protein C activation, PF4 is shown here to inhibit activation of TAFI by throm

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

221 Platelet factor 4 (PF4) is a negative regulator of megakaryopoiesis, but it

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

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

224 rmed stronger complexes than RTO, but not to PF4(K50E) dimers.

225 We demonstrated previously that a variant PF4(K50E) forms dimers but does not tetramerize or form

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

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

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

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

230 a second independent signal regulating serum PF4 levels (conditional P value: African Americans=0.02,

231 The strongest association with serum PF4 levels was observed for rs168449, which was signific

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

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

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

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

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

237 using hemophilia A plasma, NAc-Hep prevented PF4-mediated inhibition of TAFI activation and the antif

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

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

240 Thus, PF4 modulates the substrate specificity of the thrombin-

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

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

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

244 identified small molecules predicted to bind PF4 near the dimer-dimer interface and that interfere wi

245 lopment, including c-mpl, gpIIb, gpIV, gpIX, PF4, NF-E2, MafG, and Rab27B.

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

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

248 expression was able to limit the effects of PF4 on megakaryopoiesis.

249 To block the inhibitory effects of PF4 on TAFI activation, heparin derivatives were tested

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

251 We observed that although PF4 or anti-PF4 antibody alone did not alter neutrophil

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

253 formation in bone marrow isolated from human PF4-overexpressing mice (hPF4(High)).

254 gest that type IV pili are the receptors for Pf4 phage and that the essential activities of MvaT and

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

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

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

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

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

260 The Pf4 population diversified with an evolutionary rate of

261 Tetrameric PF4 potentiates aPC generation by formation of complexes

262 , 1.16-1.56) and one downstream of the genes PF4/PPBP/CXCL5 (rs1595009, P = 1.3 x 10(-4); OR, 1.32; 9

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

264 PF4 rapidly accumulates only within infected erythrocyte

265 A part of LPS is exposed, induce epitopes on PF4 resembling those on PF4/heparin complexes as shown b

266 These studies extend our understanding of PF4's negative paracrine effect in megakaryopoiesis and

267 d so we tested this receptor's importance in PF4's role in megakaryopoiesis.

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

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

270 C generation depends on the concentration of PF4 suggest similarity between PF4/CS complexes and thos

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 imer-dimer interface and that interfere with PF4 tetramerization.

276 nstrated KKO was 8-fold more reactive toward PF4 tetramers and formed stronger complexes than RTO, bu

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

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

279 xes (ULCs) of heparin and platelet factor 4 (PF4) tetramers.

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

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

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

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

284 HIT antibodies reduced the ability of PF4 to augment aPC formation.

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

286 omplexes occurs at a specific molar ratio of PF4 to glycosaminoglycan.

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

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

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

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

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

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

293 in African Americans, we found an additional PF4 variant (rs8180167), uncorrelated with rs168449 and

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

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

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

297 Four genes (CXCL16, ZNF331, JUN and PF4), which we previously identified by microarray and c

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

299 Interactions of PF4 with Gram-negative bacteria, where only the lipid A

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

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