ライフサイエンスコーパス: alpha granule

1 ting that TFPI is not stored within platelet alpha granules.

2 ng FV is found in plasma and within platelet alpha granules.

3 nhibited secretion of dense granules but not alpha granules.

4 , a basic protein found normally in platelet alpha granules.

5 (TS1), the most abundant protein of platelet alpha granules.

6 cytoplasmic membranes and reduced numbers of alpha granules.

7 cytoplasm and Dock7 on the membrane of or in alpha-granules.

8 the trans-Golgi network, late endosomes and alpha-granules.

9 s characterized by large platelets that lack alpha-granules.

10 ion requires release of stored proteins from alpha-granules.

11 odies packed with respiring mitochondria and alpha-granules.

12 n platelets and megakaryocytes and stored in alpha-granules.

13 re demonstrated, as was its association with alpha-granules.

14 delivered both in the plasma and in platelet alpha-granules.

15 rs and inhibitors into separate and distinct alpha-granules.

16 along with CD62P, into both MK and platelet alpha-granules.

17 VIII can be expressed and stored in platelet alpha-granules.

18 is accompanied by uptake of fibrinogen into alpha-granules.

19 diathesis and a marked reduction in platelet alpha-granules.

20 secretion of plasma fibrinogen from platelet alpha-granules.

21 inogen) and then package these proteins into alpha-granules.

22 bitor, a trace protein contained in platelet alpha-granules.

23 been immunized with purified human platelet alpha-granules.

24 in a rapidly releasable form within platelet alpha-granules.

25 leads to degradation of most proteins of the alpha-granules.

26 acrothrombocytopenia, with platelets lacking alpha-granules.

27 in that traffics FVIII more effectively into alpha-granules.

28 t a marked defect in exocytosis of delta and alpha granules, alphaIIbbeta3 activation, actin assembly

29 dense granule secretion; and (3) diminished alpha granule and lysosome secretion might contribute to

30 n microscopy, we confirmed that CD154 was an alpha granule and not a cell surface protein, and therea

31 P-1 helps to sequester TGF-beta1 in platelet alpha granules and activates TGF-beta1 once both protein

32 hibited platelet secretion of both dense and alpha granules and the secretion-dependent platelet aggr

33 caused increased platelet CD62P expression, alpha-granule and dense granule release, and the classic

34 tion, integrin alphaIIbbeta3 activation, and alpha-granule and dense granule secretion in response to

35 oprotein IIb or in embryos in which platelet alpha-granule and dense granule secretion is abolished.

36 elet exocytosis and differentially regulates alpha-granule and dense granule secretion.

37 hat mimic NSF sequence motifs inhibited both alpha-granule and dense-granule secretion in permeabiliz

38 ine signal to potentiate platelet release of alpha-granule and lysosome cargo and protein disulfide i

39 Ehrlich described the features of the alpha-granule and the cell's distribution in various spe

40 von Willebrand factor (VWF) is stored within alpha-granules and accounts for approximately 20% of tot

41 These platelets have few alpha-granules and an increased number of lysosomal-like

42 es can enable the storage of FIX in platelet alpha-granules and corrects the murine hemophilia B phen

43 a patient with gray platelet syndrome lacked alpha-granules and demonstrated only minimal spreading.

44 llagen were able to secrete contents of both alpha-granules and dense granules and generate thromboxa

45 to establish how cargos are segregated among alpha-granules and determine whether or not different al

46 n; (2) significant decreases of secretion of alpha-granules and GPIIb-IIIa activation induced by aden

47 ranules was completely ablated and that from alpha-granules and lysosomes was severely compromised.

48 2alpha inactivation have critical defects in alpha-granules and membrane structure that are associate

49 disorder characterized by platelets lacking alpha-granules and progressive marrow fibrosis.

50 in high concentrations of TGF-beta1 in their alpha-granules and release it on platelet adhesion/activ

51 ne megakaryocytes, it was stored in platelet alpha-granules and released at sites of injury.

52 oagulation factor V (FV) from the media into alpha-granules and releases functional FV(+)CD42b(+) hum

53 FIX can be expressed and stored in platelet alpha-granules and that platelet-derived FIX can correct

54 rombocytopenia, and a deficiency of platelet alpha-granules and their cargo, including von Willebrand

55 developing megakaryocytes would be stored in alpha-granules and whether its release from circulating

56 quired for release from dense core granules, alpha granules, and lysosomes.

57 ribution of the demarcation membrane system, alpha-granules, and other cytoplasmic organelles.

58 gray platelet syndrome platelets, which lack alpha-granules, and Wiskott-Aldrich syndrome platelets,

59 Proteins stored in alpha-granules are also thought to play a role in inflam

60 alpha-granules are by far the most abundant platelet gra

61 These observations suggest that the alpha-granules are correctly assembled but the contents

62 uring spreading, supporting the premise that alpha-granules are heterogeneous and demonstrating that

63 arrow megakaryocytes, which store FBG in the alpha-granules, are thought not to express the FBG genes

64 S stimulates platelet secretion of dense and alpha granules as indicated by ATP release and P-selecti

65 eptolysin O-permeabilized platelets released alpha-granules, as measured by surface expression of P-s

66 e defect, demonstrating a role for VPS16B in alpha-granule biogenesis and taking us one step closer t

67 characteristics of human GPS, with defective alpha-granule biogenesis in MKs and their absence from p

68 lta-granule development, less is known about alpha-granule biogenesis.

69 regulator of the genes required for platelet alpha-granule biogenesis.

70 (T2), and studied the platelet phenotype and alpha-granule biogenesis.

71 ndently of VPS33B/VPS16B at a later stage of alpha-granule biogenesis.

72 is essential for megakaryocyte and platelet alpha-granule biogenesis.

73 Sec1/Munc18 protein VPS33B are required for alpha-granule biogenesis.

74 PF4 is stored in platelet alpha-granules bound to the glycosaminoglycan (GAG) chai

75 1 indicate that TLT-1 is not simply cargo of alpha-granules but may instead regulate granule construc

76 telet factor 4 (PF4) is an abundant platelet alpha-granule C-X-C chemokine that has weak chemotactic

77 used to quantify the release of 28 distinct alpha-granule cargo molecules.

78 w that platelets can orient their release of alpha-granule cargo to promote spreading beyond the dot'

79 in and collagen increased exosome content of alpha-granule chemokines CXCL4 and CXCL7 and cytoplasmic

80 This study demonstrates that platelet alpha-granule constituents are critically required not o

81 ting that both releasable and membrane-bound alpha-granule constituents were absent.

82 Platelet alpha-granules constitute the major rapidly releasable r

83 s on liver regeneration are unclear, because alpha-granules contain bioactive molecules with opposing

84 platelet alpha-granules, unusual stimulated alpha granule content release, abnormal lipid inclusions

85 ted that platelets selectively release their alpha-granule content dependent on the environmental sti

86 studies have demonstrated a process by which alpha-granule contents are released from platelets.

87 latelets even though all dense core and most alpha-granule contents had been released.

88 pha-granule exocytosis and deposition of the alpha-granule contents such as fibrinogen and fibronecti

89 He speculated correctly that the alpha-granule contents were secretory products and descr

90 ith syntaxin-4 and promoted the secretion of alpha-granule contents, including TGF-beta and CCL5.

91 sponsible for efficient release of dense and alpha-granule contents; thus, VAMP-8(-/-) mice are a use

92 the hypothesis that distinct populations of alpha-granules could undergo selective release.

93 ) platelets identified a marked reduction in alpha-granule count and the presence of small granule-li

94 In addition, a platelet/megakaryocyte alpha granule defect, similar to that of patients with g

95 platelets from patients with an inheritable alpha-granule defect, demonstrating a role for VPS16B in

96 ult of the characterization of patients with alpha-granule deficiencies.

97 In addition, we demonstrate that alpha-granule deficiency impairs platelet function beyon

98 irment in MVB maturation in MKs underlie the alpha-granule deficiency in Vps33b(fl/fl)-ER(T2) mouse a

99 for aggregation, and gray platelet syndrome alpha-granule-deficient platelets do not aggregate to 4

100 er associated with macrothrombocytopenia and alpha-granule-deficient platelets.

101 We previously showed that platelet (PLT) alpha granule-delivered urokinase plasminogen activator

102 oG(-/-) platelets was reduced secretion from alpha-granules, dense granules, and lysosomes following

103 We measured plasma levels of alpha-granule-derived factors in the liver vein at the e

104 n combination with the loss of proteins from alpha-granules drives the development of bone marrow fib

105 Thus, release of thrombospondin-1 from alpha-granules during activation provides positive feedb

106 )](i), but it is specifically coupled to the alpha-granule exocytic pathway without concomitant effec

107 alpha Granule exocytosis from VAMP-7(-/-) platelets was

108 Interestingly, alpha-granule exocytosis and deposition of the alpha-gra

109 Time-lapse microscopy demonstrated that alpha-granules expressing VAMP-7 actively moved from the

110 In contrast, alpha-granules expressing VAMP-7 translocated to the per

111 may be caused by an abnormality in platelet alpha-granule factor V distinct from that described for

112 ith collagen and thrombin express functional alpha-granule factor V only on a subpopulation of cells.

113 vesicle trafficking pathways responsible for alpha-granule formation are beginning to be assembled as

114 nction, and they also indicate that abnormal alpha-granule formation in Nbeal2(-/-) mice has deleteri

115 les with increased size as compared with the alpha-granules from control mouse platelets.

116 s of dense granules, lysosomal granules, and alpha-granules from human platelets by S-nitrosylation o

117 pha-granule secretion that include homotypic alpha-granule fusion and the fusion of alpha-granules wi

118 -FV platelets may explain the unique role of alpha-granule FV and the hemostatic effectiveness of you

119 s express very high levels of surface-bound, alpha-granule FV on simultaneous activation with 2 agoni

120 regulates not only megakaryopoiesis but also alpha-granule generation and signaling pathways required

121 Factor V (FV) present in platelet alpha-granules has a significant but incompletely unders

122 escribe cells with granules (which he called alpha-granules) having an affinity for eosin and other a

123 telet factor 4 (PF4) is an abundant platelet alpha-granule heparin-binding protein.

124 ltimate secretion; (2) impaired secretion of alpha granules in HPS, and to some degree of lysosomes,

125 servoirs within the vascular endothelium and alpha granules in platelets.

126 leeding diathesis characterized by a lack of alpha granules in platelets.

127 bleeding disorder caused by a deficiency of alpha granules in platelets.

128 atients' fibroblasts and by the depletion of alpha granules in their platelets.

129 duced platelet aggregation; and large, fused alpha-granules in 1% to 5% of circulating platelets.

130 and morphologically distinct populations of alpha-granules in megakaryocytes and platelets may provi

131 rombocytopenia, splenomegaly, and paucity of alpha-granules in megakaryocytes and platelets.

132 Fourth, an unanticipated role for alpha-granules in platelet spreading has been identified

133 are separated in distinct subpopulations of alpha-granules in platelets and megakaryocytes.

134 rized by thrombocytopenia and the absence of alpha-granules in platelets.

135 REM-like transcript-1, which is localized to alpha-granules in resting platelets, binds fibrinogen, a

136 in protein, SEPT5, to the presence of larger alpha-granules in the GP Ibbeta(Null) platelet.

137 ed that platelet FVIII is stored in platelet alpha-granules independent of the presence of VWF.

138 is and elaboration of TGF-beta from platelet alpha-granules into the circulation.

139 y antagonistic functions are packaged within alpha-granules is controversial.

140 odel of GPS and demonstrate that the lack of alpha-granules is due to their loss from platelets/matur

141 l levels and were appropriately localized to alpha-granule-like structures.

142 red PDI secretion and impaired exocytosis of alpha granules, lysosomes, and T granules due to decreas

143 rder characterized by deficiency of platelet alpha-granules, macrothrombocytopenia and marrow fibrosi

144 number, as well as maximal secretion of the alpha-granule marker P-selectin; however, their capacity

145 s), and with S12 antibody (to P-selectin, an alpha-granule membrane protein expressed on the platelet

146 The platelet alpha-granule membrane protein P-selectin is expressed a

147 Because alpha-granule molecules are stored in separate compartme

148 , we investigated the pattern of circulating alpha-granule molecules during liver regeneration in 157

149 Secretion of alpha granules (monitored by flow cytometric measurement

150 al platelet counts, platelet morphology, and alpha-granule number, as well as maximal secretion of th

151 olipase A2 (sPLA2) is an enzyme found in the alpha granules of platelets and at inflammatory sites.

152 ke growth factor-1 (IGF-1) is present in the alpha granules of platelets and its receptor is expresse

153 Megakaryocyte-derived VWF is stored in alpha-granules of platelets and is enriched in hyperacti

154 id not affect the sorting of P-selectin into alpha-granules of platelets but severely compromised the

155 This indispensable cofactor is stored in alpha-granules of platelets via a poorly understood endo

156 FVIII in megakaryocytes, with storage in the alpha-granules of platelets, has the advantage of delive

157 e most abundant protein contained within the alpha-granules of platelets, is a broad-spectrum inhibit

158 In this study, we show that ATX is stored in alpha-granules of resting human platelets and released u

159 the effects of factors derived from platelet alpha-granules on liver regeneration are unclear, becaus

160 studies, whereas STX8 was not essential for alpha-granule or lysosome secretion, Stx8(-/-) platelets

161 T (dense core granules), platelet factor IV (alpha granules), or hexosaminidase (lysosomes) between n

162 onal agonists and antagonists into different alpha-granule populations.

163 V is highly concentrated within the platelet alpha-granule, previous analysis of human bone marrow an

164 he structure, function, and formation of the alpha-granule protein "coat." Confocal microscopy reveal

165 Platelet factor 4 (PF4), a platelet alpha-granule protein and a soluble cofactor for TM-depe

166 phosphatidylserine (PS) surface expression, alpha-granule protein retention, and lack of active inte

167 latelet factor 4 (PF4), an abundant platelet alpha-granule protein, accelerates in vitro generation o

168 without affecting the release of betaTG, an alpha-granule protein.

169 PN-2 is known to be an abundant platelet alpha-granule protein.

170 reas we observed deficiency of megakaryocyte alpha-granule proteins and emperipolesis.

171 are characterized by high surface levels of alpha-granule proteins and phosphatidylserine, which sup

172 adequate packaging and secretion of selected alpha-granule proteins and reduced secretion of dense gr

173 alpha-Granule proteins bound to COAT-platelets are deriv

174 r-wise comparisons of 15 angiogenic-relevant alpha-granule proteins displayed little, if any, pattern

175 -1 is stabilized by its packaging with other alpha-granule proteins in a calcium-dependent manner.

176 Fractionation of alpha-granule proteins on molecular sieving columns usin

177 ceptionally strong retention of procoagulant alpha-granule proteins on the surface of COAT platelets.

178 The alpha-granule proteins platelet factor 4, beta-thrombogl

179 taining revealed 25-nm diameter complexes of alpha-granule proteins under the electron microscope.

180 approximately 65% to 75% was observed in the alpha-granule proteins von Willebrand factor and P-selec

181 Other alpha-granule proteins were expressed at normal levels a

182 Soluble and membrane-bound alpha-granule proteins were reduced or undetectable, sug

183 riety of monoclonal antibodies show that the alpha-granule proteins, fibrinogen, von Willebrand facto

184 high levels of phosphatidylserine and retain alpha-granule proteins, including fibrinogen, on their s

185 rred to as 'COAT-platelets', bind additional alpha-granule proteins, including fibrinogen, von Willeb

186 ediated conjugation of serotonin to released alpha-granule proteins.

187 Moreover, thrombin-induced platelet alpha-granule release as well as release of adenosine tr

188 dy to syntaxin 4 also inhibited Ca2+-induced alpha-granule release by approximately 75% in this syste

189 Selective modulation of platelet alpha-granule release in patients may represent an attra

190 lets showed enhanced integrin activation and alpha-granule release in response to stimulation of (hem

191 sembles with activation and demonstrate that alpha-granule release is dependent on vesicle SNAP recep

192 Patients with an unfavorable postoperative alpha-granule release profile (high TSP-1/low VEGF) show

193 The unfavorable postoperative alpha-granule release profile was associated with increa

194 isoform, the Pro(33) variant showed greater alpha-granule release, clot retraction, and adhesion to

195 Es and that actin polymerization facilitates alpha-granule release.

196 ne protein completely inhibited Ca2+-induced alpha-granule release.

197 The major platelet organelles, alpha-granules, release proteins that participate in thr

198 Although alpha granules released their contents through both mode

199 en recent controversy as to whether platelet alpha-granules represent a single granule population or

200 acrothrombocytopenia and absence of platelet alpha-granules resulting in typical gray platelets on pe

201 nd type 1 plasminogen activator inhibitor in alpha-granule-rich fractions.

202 We show that alpha granule secretion elicited by low agonist doses is

203 rt a mechanism whereby the reported enhanced alpha granule secretion in the Pro(33)-positive platelet

204 surface expression of P-selectin (reflecting alpha granule secretion); (ii) exposure of the fibrinoge

205 global, because other activation responses, alpha granule secretion, shape change, and aggregation w

206 enosine 5'-diphosphate (ADP) restored normal alpha granule secretion, suggesting that the impairment

207 accumulation and affirmed a reduced area of alpha granule secretion.

208 ly inhibits thrombin peptide (SFLLR)-induced alpha-granule secretion (IC(50) = 20 microM) during the

209 TGF-beta1 release is dissociated from alpha-granule secretion (P-selectin up-regulation) and o

210 ma2, leading to downstream responses such as alpha-granule secretion and activation of integrin alpha

211 show that PtdIns(4,5)P(2) mediates platelet alpha-granule secretion and that PtdIns(4,5)P(2) synthes

212 8220 completely inhibited platelet dense and alpha-granule secretion at a concentration of 20 microM

213 GPVI and PAR-induced aggregation, dense and alpha-granule secretion at low agonist concentrations.

214 s of latrunculin A inhibited agonist-induced alpha-granule secretion but stimulated dense granule sec

215 Inhibition of alpha-granule secretion by antihuman cellubrevin was rev

216 ellubrevin antibody inhibited Ca(++)-induced alpha-granule secretion by approximately 50%.

217 inhibited both PtdIns(4,5)P(2) synthesis and alpha-granule secretion by approximately 50%.

218 PtdIns(4,5)P(2) synthesis and Ca(2+)-induced alpha-granule secretion by approximately 50%.

219 SFLLRN-stimulated alpha-granule secretion from SL-O-permeabilized platelet

220 osphate 4-kinase augmented SFLLRN-stimulated alpha-granule secretion from SL-O-permeabilized platelet

221 membrane protein and inhibited Ca2+-induced alpha-granule secretion from streptolysin O-permeabilize

222 Inhibition of actin polymerization prevented alpha-granule secretion in this system, and purified pla

223 ctin cytoskeleton by latrunculin A inhibited alpha-granule secretion induced by several different pla

224 5)P(2) synthesis required for Ca(2+)-induced alpha-granule secretion involves the type II phosphatidy

225 the possibility that morphologic features of alpha-granule secretion may be influenced by the subcell

226 These antibodies inhibited alpha-granule secretion only when added prior to ATP exp

227 Our results confirm that alpha-granule secretion plays a significant role in plat

228 vides a basis for several characteristics of alpha-granule secretion that include homotypic alpha-gra

229 SFLLRN-stimulated alpha-granule secretion was inhibited by a protein kinas

230 Phorbol 12-myristate 13-acetate-stimulated alpha-granule secretion was inhibited by anti-type II Pt

231 Latrunculin A-dependent alpha-granule secretion was inhibited by antibodies dire

232 creases in [Ca(++)](i), Rap1 activation, and alpha-granule secretion were unaffected.

233 leration and augmentation of agonist-induced alpha-granule secretion with comparatively modest effect

234 tion of the matrix itself regulates platelet alpha-granule secretion, a key component of platelet act

235 asured by integrin alphaIIbbeta3 activation, alpha-granule secretion, and procoagulant activity.

236 sure of platelet factor XI is independent of alpha-granule secretion, because ADP and collagen expose

237 In addition to stimulating alpha-granule secretion, both SFLLRN and PMA enhanced th

238 bserved that platelet DREAM is important for alpha-granule secretion, Ca(2+) mobilization, and aggreg

239 platelets fail to spread and have decreased alpha-granule secretion, integrin alphaIIbbeta3 activati

240 ulated through GPVI, resulting in defects in alpha-granule secretion, integrin alphaIIbbeta3 activati

241 ying platelet aggregation, dense granule and alpha-granule secretion, P-selectin expression, micropar

242 dIns 3-kinase did not inhibit Ca(2+)-induced alpha-granule secretion, suggesting that PtdIns 3-kinase

243 rmine whether these proteins are involved in alpha-granule secretion, we developed a streptolysin O-p

244 Exogenously added PtdIns(4,5)P(2) inhibited alpha-granule secretion, with 80% inhibition at 50 micro

245 d substitute for platelet cytosol to support alpha-granule secretion.

246 ry system, platelet cytosol was required for alpha-granule secretion.

247 guanosine triphosphate (GTP)-gamma-S-induced alpha-granule secretion.

248 let function, causing stable aggregation and alpha-granule secretion.

249 osphate 4-kinase in agonist-induced platelet alpha-granule secretion.

250 strated that SNARE proteins are required for alpha-granule secretion.

251 reorganization, adhesion to fibrinogen, and alpha-granule secretion.

252 ting that PtdIns 3-kinase is not involved in alpha-granule secretion.

253 time-dependent inhibition of Ca(2+)-induced alpha-granule secretion.

254 ositol 4,5-bisphosphate (PtdIns(4,5)P(2)) in alpha-granule secretion.

255 membrane protein, SNAP-23, and syntaxin 4 in alpha-granule secretion.

256 reptolysin O-permeabilized platelet model of alpha-granule secretion.

257 ntiation of myofibroblasts in the absence of alpha-granule secretion.

258 te SEPT5 levels in the maintenance of normal alpha-granule size and may explain the variant granules

259 Electron microscopy revealed normal alpha-granule structure in SG-/- platelets.

260 nules and determine whether or not different alpha-granule subpopulations exist in platelets.

261 These studies identify a new alpha-granule subtype expressing VAMP-7 that moves to th

262 Individuals whose platelets lack dense or alpha-granules suffer various degrees of abnormal bleedi

263 pecifically accumulated fibronectin in their alpha-granules, suggesting that fibronectin could be the

264 s more evenly distributed among membranes of alpha-granules, the open canalicular system, and plasma

265 openia with large platelets and a paucity of alpha-granules; these abnormalities cause mostly moderat

266 ation of HYAL2 from a distinct population of alpha-granules to platelet surfaces where it exerts its

267 ts actively sort a specific subpopulation of alpha-granules to the periphery during spreading.

268 zed platelet abnormalities (reduced platelet alpha-granules, unusual stimulated alpha granule content

269 se insulin-like growth factor-1 (IGF-1) from alpha granules upon activation.

270 onectin/PAI-1 complexes were not detected in alpha-granules using a two-site immunoassay.

271 wed similar ultra-structure characteristics (alpha granules, vacuoles and dense tubular system) as PL

272 Addition of calcium ions to intact alpha-granules was an effective means of neutralizing th

273 y of PAI-1 in both platelets and in isolated alpha-granules was prolonged in comparison to the rapid

274 ibodies derived from a rabbit immunized with alpha-granules, was subcloned into the prokaryotic expre

275 Proteins that are normally stored in alpha-granules were underrepresented in MVB II and propl

276 count and P-selectin (a ubiquitous cargo of alpha-granules) were not associated with postoperative l

277 other major platelet granules, lysosomes and alpha granules, were apparent.

278 on microscopy revealed a complete absence of alpha-granules, whereas delta-granules were observed.

279 h isoforms are expressed in resting platelet alpha-granules, which are up-regulated to the cell surfa

280 Co-incubation of alpha-granules with a number of agents that disrupt pH g

281 ombospondin-1 (TSP-1) purified from platelet alpha-granules with an apparent K(D) of approximately 7.

282 duced by a GP Ibbeta(Null) genotype revealed alpha-granules with increased size as compared with the

283 ity of PAI-1 activity, whereas incubation of alpha-granules with the calcium ionophore A23187 reduced

284 typic alpha-granule fusion and the fusion of alpha-granules with the open canalicular system and plas

285 Megakaryocytes store BDNF in alpha-granules, with more than 80% of them also containi

286 bleeding disorder characterized by a lack of alpha-granules within blood platelets and progressive bo

287 as associated with uptake of fibrinogen into alpha-granules without surface binding despite pretreatm