ライフサイエンスコーパス: alpha4 integrin

1 herent cells, where it also colocalizes with alpha4 integrin.

2 early progenitor expansion in the absence of alpha4 integrin.

3 the avidity of cell adhesion mediated by the alpha4 integrin.

4 s replaced by the cytoplasmic portion of the alpha4 integrin.

5 mal controls and no detectable expression of alpha4 integrin.

6 NF-alpha, all of which was blocked by mAb to alpha4 integrin.

7 CS1, because of decreased expression of the alpha4 integrin.

8 hereby controlling the abundance of unpaired alpha4 integrin.

9 rophages, an association mediated in part by alpha4 integrin.

10 pinal cord by blocking the adhesion molecule alpha4-integrin.

11 ic CD4(+) T cells to the CNS is dependent on alpha4 integrins.

12 n inflammatory sites are mediated in part by alpha4 integrins.

13 n flow and rolling interactions through both alpha4 integrins.

14 to the lung using beta2 rather than beta1 or alpha4 integrins.

15 LFA-1 (lymphocyte-associated antigen 1) and alpha4 integrins.

16 r, spleen, and bone marrow can occur without alpha4 integrins.

17 is carinatus venom is a potent antagonist of alpha4 integrins.

18 al killer cells can develop normally without alpha4 integrins.

19 ing animals with natalizumab, which binds to alpha4-integrins.

20 tivates integrin-linked kinase 1 (ILK-1) via alpha4-integrins.

21 Mast cells express alpha4 integrins -- a potential mechanism for adhesion t

22 Therefore, our data suggest that anti-alpha4 integrin Ab treatment may be more efficient in th

23 ted Tie2Cre+alpha4(f/f) mice with documented alpha4-integrin ablation in hematopoietic and endothelia

24 hrough heat shock protein 90 (Hsp90)-induced alpha4 integrin activation and signaling in T cells.

25 The alpha4 integrin adhesion receptor is associated with enh

26 Thus therapeutic targeting of alpha4 integrins affects DC trafficking into the CNS and

27 aracterized mice bearing a Y991A mutation in alpha4 integrin [alpha4(Y991A) mice], which blocks paxil

28 sely related to the alpha4 subunit, and like alpha4 integrins, alpha9beta1 plays an important role in

29 These data reveal a direct link between the alpha4 integrin and actin polymerization and uncover a r

30 nd have shown the inhibitory effects of anti-alpha4 integrin and anti-vascular cell adhesion molecule

31 B and T lymphocytes into BALT, whereas anti-alpha4 integrin and anti-VCAM-1 mAbs inhibit homing by n

32 These data demonstrate that alpha4 integrin and ICAM-1 play major roles in the recru

33 Blocking interactions between alpha4 integrin and its ligands may provide novel forms

34 ects of blockade of the interactions between alpha4 integrin and its ligands, vascular cell adhesion

35 that T helper (Th)1 and Th2 lymphocytes use alpha4 integrin and vascular adhesion protein (VAP)-1, r

36 esults indicate that the interaction between alpha4 integrin and VCAM-1 is important for sympathetic

37 Importantly, we found that mAbs against alpha4 integrin and VCAM-1 significantly block the migra

38 0.5 and 2.0 dynes/cm2 could be attributed to alpha4 integrin and VCAM-1.

39 By flow cytometry, expression of alpha4 integrins and a beta1 integrin activation epitope

40 peptide CWLDVC (TBC 772) is an antagonist of alpha4 integrins and a potent inhibitor of lymphocyte in

41 lamed and inflamed glomeruli using beta2 and alpha4 integrins and CX3CR1.

42 In addition, mAb blockade of the alpha4 integrins and targeted deletion of an alpha(1,3)f

43 se being dependent on an interaction between alpha4 integrins and VCAM-1.

44 The coordination between the extension of alpha4-integrin and its affinity provides a mechanism fo

45 th groups expressed CXCR3, CCR5, L-selectin, alpha4 integrins, and cutaneous lymphocyte antigen.

46 ptide donor, which specifically binds to the alpha4-integrin, and octadecyl rhodamine B acceptors inc

47 dhesion to IL-4-activated HUVECs was totally alpha4-integrin- and VCAM-1-dependent.

48 Natalizumab is an alpha4 integrin antagonist that reduced the development

49 Natalizumab, an alpha4 integrin antagonist, appeared to be safe and effe

50 ined the effects of a monoclonal antibody to alpha4 integrin (anti-alpha4 Ab) that disrupts myeloma c

51 istration of anti-alpha4beta7 integrin, anti-alpha4 integrin, anti-beta7 integrin, or anti-MAdCAM-1 m

52 by alpha4beta1 integrin because soluble anti-alpha4 integrin antibodies inhibited Hep II domain-media

53 Although both anti-alpha4 integrin antibody and CS1-peptide completely abol

54 Conversely, anti-alpha4 integrin antibody and CS1-peptide may prevent isl

55 for inhibiting relapses, the humanized anti-alpha4 integrin antibody known as Natalizumab, blocks ho

56 In contrast to anti-VAP-1, anti-alpha4 integrin antibody reduced interferon-gamma (IFN-g

57 significantly less in mice treated with anti-alpha4 integrin antibody than in those treated with cont

58 Treatment with anti-alpha4 integrin antibody, anti-VCAM-1 antibody, or with

59 th tachyzoites were markedly greater in anti-alpha4 integrin antibody-treated than in control antibod

60 Natalizumab, an anti-alpha4-integrin antibody, binds to T-cell surface recept

61 However, it is uncertain whether alpha4 integrins are also required for the migration of

62 Alpha4 integrins are essential for definitive hematopoie

63 alpha4 integrins are essential for embryogenesis, hemato

64 In summary, alpha4 integrins are essential for normal development of

65 We also show that alpha4 integrins are essential for T cell homing to Peye

66 alpha4 integrins are important mediators of leukocyte mi

67 The alpha4 integrins are indispensable for embryogenesis, ha

68 ines reveals that alpha(v)beta3, alpha5, and alpha4 integrins are sensitive to Amino-Nogo, but alpha6

69 Moreover, alpha4 integrins are shown to be integral to a CHS but n

70 alpha4 integrins are type I PKA-specific A-kinase anchor

71 Cellular fibronectin and VCAM-1, ligands for alpha4 integrins, are enriched in the fluid of airways o

72 id differentiation, we identified band 3 and alpha4 integrin as optimal surface markers for isolating

73 cZalpha4AS) that expresses antisense chicken alpha4-integrin as the 3' untranslated region of a lacZ

74 Our findings identify the Hsp90-alpha4-integrin axis as a thermal sensory pathway that p

75 uthors report that the binding of sVCAM-1 to alpha4 integrin-bearing cells is a dynamically regulated

76 iological level of shear stress, endothelial alpha4 integrins became phosphorylated on Ser(988).

77 A crystal structure of the Fab bound to an alpha4 integrin beta-propeller and thigh domain fragment

78 change in the FXIII-A protein that enhances alpha4-integrin binding and provides insight into an une

79 Furthermore, alpha4 integrin blockade abrogated the chemerin-dependen

80 Combined beta2 integrin deficiency and alpha4 integrin blockade also did not affect the GC resp

81 Furthermore, alpha4 integrin blockade reduced the trafficking of the

82 etween control and EVL/VASP dKO T cells upon alpha4 integrin blockade.

83 Cytotrophoblasts expressing alpha4 integrins bound immobilized VCAM-1 in vitro, sugg

84 By inducing selective binding of Hsp90 to alpha4 integrins, but not beta2 integrins, fever increas

85 We therefore hypothesized that ligands of alpha4 integrins can promote eosinophil survival indepen

86 f EVL and VASP resulted in the impairment in alpha4 integrin (CD49d) expression and function.

87 zed mice was used to address the role of the alpha4 integrin (CD49d) in mediating the airway inflamma

88 t here that transient, ectopic expression of alpha4 integrin (CD49d) on MSC greatly increases bone ho

89 ke protein (PODXL), alpha6-integrin (CD49f), alpha4-integrin (CD49d), c-Met, CXCR4, and CX3CR1.

90 development by transplantation of embryonic alpha4 integrin(-/-) cells into the adult microenvironme

91 Finally, alpha9beta1 and alpha4 integrins contribute to neutrophil chemotaxis acr

92 Alpha4 integrins contribute to the development of HFD-in

93 LFA-1, but not alpha4 integrins, contributed to B-cell motility in PLNs

94 The ability of the alpha4 integrin counterligands vascular cell adhesion mo

95 a dense peri-islet infiltrate of activated, alpha4 integrin+, cytotoxic T cells.

96 In a noncompetitive setting, alpha4 integrin deficiency on monocyte-derived DCs was f

97 n small intestine and colon, the fraction of alpha4 integrin-deficient CD11b(+)CD103(+) DCs was selec

98 e both before and after irradiation, and (4) alpha4 integrin-deficient cells not only lodge with redu

99 n as LysM), respectively, the recruitment of alpha4 integrin-deficient conventional and plasmacytoid

100 ional-knockout mouse model, and we show that alpha4 integrin-deficient hematopoietic progenitor cells

101 omic partitioning of transplanted normal and alpha4 integrin-deficient Lin-kit+ cells in trabecular a

102 We show that the cranial vessels in alpha4 integrin-deficient mouse embryos at the stage of

103 ytoid DCs to the CNS was unaffected, whereas alpha4 integrin-deficient, monocyte-derived DCs accumula

104 red the functional implications of inducible alpha4 integrin deletion during adult hematopoiesis by g

105 w, but both domains 1 and 4 were utilized in alpha4 integrin-dependent adhesion under static conditio

106 pha4 integrins with consequent regulation of alpha4 integrin-dependent cellular functions.

107 gulated and that this regulation may control alpha4 integrin-dependent cellular functions.

108 esis step of transendothelial migration in a alpha4 integrin-dependent manner.

109 /IFN-gamma-pretreated vessels in vivo via an alpha4 integrin-dependent pathway.

110 omain 1 of VCAM-1 was solely responsible for alpha4 integrin-dependent primary capture under flow, bu

111 rast, in vivo blocking of beta1 integrins or alpha4 integrins did not affect lung ILC2 numbers.

112 Anti-alpha4 integrin dramatically blocked the influx of MDSCs

113 er groups suggest a specific requirement for alpha4 integrin during the fetal/neonatal stages of HSC

114 We investigated roles of alpha4 integrins during hematopoiesis using mutant and c

115 Use of band 3 and alpha4 integrin enabled us to isolate erythroblasts at s

116 romote an environment that is indifferent to alpha4 integrin expression by DCs.

117 In contrast, alpha4 integrin expression is important for Th1 cells to

118 n alphad levels by 3-7 d without a change in alpha4 integrin expression.

119 Precursors for both T and B cells require alpha4 integrins for normal development within the bone

120 results show that eotaxin-2 rapidly reduced alpha4 integrin function while increasing beta2 integrin

121 ted a knockin mutation in mice replacing the alpha4 integrin gene with the lacZ reporter gene, placin

122 Our findings show that VAP-1 and alpha4 integrin have opposing effects in Con A-induced h

123 mation, and immune response possibly because alpha4 integrins have distinct signaling properties from

124 The SLAYGLR-mediated alpha4 integrin/IFN-beta axis is MyD88 independent and o

125 tiation, whereas conditional inactivation of alpha4 integrin in adult mice has only subtle effects.

126 Thus, conditional deletion of alpha4 integrin in adult mice is accompanied by a novel

127 and, stem cell factor (SCF), cooperates with alpha4 integrin in inducing directed migration of mast c

128 study, we showed that selective deletion of alpha4 integrin in T cells did not prevent but delayed t

129 nflammation while sparing vital functions of alpha4 integrins in development and hematopoiesis.

130 Previous analyses of the roles of alpha4 integrins in hematopoiesis by other groups have l

131 , developmentally regulated requirements for alpha4 integrins in hematopoiesis in the bone marrow.

132 Paxillin physically associated with alpha4 integrins in Jurkat T cells at high stoichiometry

133 o investigate the roles of LFA-1, Mac-1, and alpha4 integrins in neutrophil recruitment in vivo.

134 To better understand the function of alpha4-integrin in epicardial development, we constructe

135 mice have demonstrated an essential role for alpha4-integrin in normal epicardial development, but th

136 body against the leukocyte adhesion molecule alpha4 integrin, in patients with acute ischaemic stroke

137 recombinant humanized monoclonal antibody to alpha4 integrin, in patients with mild to moderately act

138 mab, a humanized monoclonal antibody against alpha4 integrin, inhibits leukocyte adhesion and migrati

139 ha4-integrin or VCAM-1, which indicates that alpha4-integrin interacting with VCAM-1 stabilizes rolli

140 uite efficiently, because of compensation by alpha4-integrin interacting with VCAM-1.

141 Blocking alpha4 integrins interfered with the adhesion but not th

142 These data show that alpha4 integrin is critically important to allograft rej

143 The neutralization of alpha4 integrin is currently used as treatment in severa

144 The glycoprotein alpha4 integrin is expressed on the surface of these cel

145 suggest that binding of domain 1 of VCAM to alpha4-integrins is unimpeded by the Fab, and that bound

146 Natalizumab antibody to alpha4-integrins is used in therapy of multiple sclerosi

147 b, a humanized monoclonal antibody targeting alpha4 integrin, is effective against active relapsing-r

148 CD8, CD45RC, T-cell receptor (TCR) Vbeta8.2, alpha4 integrin, L-selectin, CD44, and CD134.

149 their blockade was combined with deletion of alpha4-integrin, leading to dramatic reduction in BM hom

150 Previous studies have revealed that all alpha4 integrin-ligand interactions are dependent on a k

151 d on CD82 palmitoylation and the presence of alpha4 integrin ligands.

152 nt, but the precise cellular consequences of alpha4-integrin loss remain uncertain.

153 in robust and stable long-term generation of alpha4 integrin(-/-) lymphoid and myeloid cells, althoug

154 dependent on VCAM-1, and inhibited with anti-alpha4 integrin mAb (67.7 +/- 7.5% inhibition, p < 0.000

155 ta7 on HPCs contributes to about half of all alpha4 integrin-mediated homing activity following BM tr

156 ondroitin sulfate proteoglycan- and possibly alpha4 integrin-mediated pathway, which triggers a caspa

157 ns, but not beta2 integrins, fever increased alpha4-integrin-mediated T cell adhesion and transmigrat

158 t, the intravenous administration of an anti-alpha4 integrin MoAb, HP2/1 (3.5 mg/kg), or an anti-VCAM

159 beled cells while greatly reducing levels of alpha4-integrin mRNA and protein.

160 alpha4 integrin mutant cells developing in [alpha4 integ

161 vascular repair, which could be reversed by alpha4-integrin mutation.

162 This study provides evidence that epicardial alpha4-integrin normally restrains epicardial-mesenchyma

163 stinct from the ones previously described in alpha4 integrin-null chimeras and beta1 integrin-conditi

164 ontrast to the embryonic-lethal phenotype of alpha4 integrin-null mice, mice bearing the alpha4(Y991A

165 Furthermore, cultured alpha4 integrin-null PC/pvSMCs plated on fibronectin dis

166 These studies suggest that beta1, but not alpha4, integrin of VLA-4 is the sex-specific molecule o

167 peptide corresponding to the binding site of alpha4 integrin on fibronectin (connecting segment 1 pep

168 odentium were not impaired in the absence of alpha4 integrins on DCs.

169 Binding of recombinant sVCAM-1 to alpha4 integrins on peripheral blood mononuclear cells w

170 receptors on Chinese hamster ovary cells and alpha4 integrins on rat basophilic leukemia cells showed

171 s, leading to dimerization and clustering of alpha4 integrins on the cell membrane and subsequent act

172 yolk sac, but it decreased the expression of alpha4-integrin on EMPs and compromised EMP colonization

173 otein kinase A (PKA), and phosphorylation of alpha4-integrin on serine 988.

174 fected wild-type mice were treated with anti-alpha4 integrin or control antibodies and transferred in

175 Vehicle or antibody to alpha4 integrin or VAP-1 was intravenously administered

176 monolayers is blocked by antibodies against alpha4 integrin or VCAM-1.

177 clonal antibody blockade of mononuclear cell alpha4-integrin or VCAM-1, which indicates that alpha4-i

178 1 integrin thus dominates beta7 integrin for alpha4 integrin pairing, thereby controlling the abundan

179 indings imply that both selectin ligands and alpha4 integrins participate in T lymphoblast recruitmen

180 Blocking beta2 and alpha4 integrin pathways together inhibited secondary/fi

181 hereby show that shear-induced PKA-dependent alpha4 integrin phosphorylation at the downstream edge o

182 Here we report that localized alpha4 integrin phosphorylation is a mechanism for estab

183 The shear-induced alpha4 integrin phosphorylation was blocked by inhibitor

184 ath patterns in vitro and in vivo argue that alpha4-integrins play a role in survival during cell mig

185 , or PSGL-1, whereas combinations of mAbs to alpha4-integrin plus PSGL-1, or VCAM-1 plus E-selectin,

186 erosclerosis, where it is thought to recruit alpha4 integrin-positive leukocytes, which play a role i

187 ells (VSMC) results in increased adhesion of alpha4 integrin-positive lymphocytes.

188 molecule 1 (VCAM-1) and its ligand component alpha4 integrin potently inhibited EPC adhesion to RA fi

189 gene, placing lacZ under the control of the alpha4 integrin promoter.

190 The alpha4 integrin protein, required for chorioallantoic fu

191 nt mice were treated with antibodies against alpha4 integrin (PS/2), VCAM-1 (MK 2.7), and a peptide c

192 alpha4beta7 (hybridoma clone DATK32) or anti-alpha4 integrins (PS/2).

193 The alpha4 integrin receptor may also be involved, since usi

194 kocyte-endothelium adhesion by antagonism of alpha4 integrin reduces infarct volumes and improves out

195 Such signals from alpha4 integrins regulate cell migration in development

196 preferential pairing of beta1 integrin with alpha4 integrin regulates the expression of alpha4beta7

197 Increasing the abundance of alpha4 integrin relative to beta1 integrin is critical t

198 n Junctional Adhesion Molecule-A (JAM-A) and alpha4 integrin, respectively.

199 ymphocytes via their known ligands LFA-1 and alpha4-integrin, respectively.

200 Antagonists to alpha4 integrin show promise for several autoimmune and

201 hemical data demonstrate that both c-Kit and alpha4 integrin signaling are linked to class IA PI-3kin

202 We previously proposed that blockade of alpha4 integrin signaling can inhibit inflammation while

203 ytes into adipose tissue; hence, blockade of alpha4 integrin signaling can prevent the development of

204 We conclude that interference with alpha4 integrin signaling can selectively impair mononuc

205 We tested the capacity of blockade of alpha4 integrin signaling to perturb functions involved

206 , which blocks paxillin binding and inhibits alpha4 integrin signals that support leukocyte migration

207 -1, as well as a small molecule inhibitor of alpha4 integrins, significantly reduced sympathetic inne

208 ouble-blind, placebo-controlled trial of the alpha4 integrin-specific humanized monoclonal antibody n

209 The alpha4 integrin subunit that pairs with beta7 integrin c

210 In the presence of mAb to the alpha4 integrin subunit, the effect of CCR3 mAb was more

211 1 represents a CSGAG binding site within the alpha4 integrin subunit.

212 t, and suppress the expression of CD49d, the alpha4 integrin subunit.

213 They expressed alpha5, beta1, alpha v, and alpha4 integrin subunits, known receptors for FN, and in

214 2 in regulating the membrane organization of alpha4 integrin subunits.

215 gration was inhibited by anti-VCAM-1 or anti-alpha4 integrin, suggesting that VCAM-1 adhesion was req

216 ferential association of beta1 integrin with alpha4 integrin suppresses alpha4beta7 integrin expressi

217 /14-3-3-zeta interactions, and recently, the alpha4 integrin tail was reported to bind to 14-3-3-zeta

218 We have identified a peptide from within alpha4 integrin termed SG1 (KKEKDIMKKTI) that binds to c

219 ll adhesion molecule-1 (VCAM-1), which binds alpha4 integrins that lack an I domain.

220 py of multiple sclerosis include blockade of alpha4 integrin, the use of altered peptide ligands, inh

221 ion of these progenitors is possible without alpha4 integrins, these receptors are essential to maint

222 y, these results showed that the capacity of alpha4 integrins to bind VCAM-1 is actively regulated an

223 T lymphoblasts use both selectin ligands and alpha4 integrins to enter the airspace and interstitium

224 y shown specifically inhibits the binding of alpha4 integrins to ligands, would also be a functional

225 t neutrophils, unlike other species, may use alpha4 integrins to traffic to sites of inflammation in

226 t affinity states were generated by exposing alpha4-integrins to divalent ions or by inside-out activ

227 exist between the interactions of VCAM-1 and alpha4 integrin under static and flow conditions, and th

228 ssed by leukocytes, we report that beta2 and alpha4 integrins use different RIAM-dependent and -indep

229 or expression of a phosphorylation-defective alpha4-integrin variant (alpha4[S988A]).

230 ed HUVECs was blocked by 50% by mAbs against alpha4-integrin, vascular cell adhesion molecule-1 (VCAM

231 us, PrMCs derived in vitro predominantly use alpha4-integrin, VCAM-1, PSGL-1, and other ligands that

232 Hsp90 bound to the alpha4 tail and activated alpha4 integrins via inside-out signaling.

233 osis (MS), depends on the interaction of the alpha4 integrin (VLA-4) expressed on activated T cells w

234 otechnology, my colleagues and I showed that alpha4 integrin was the critical molecule involved in th

235 A small molecule antagonist of alpha4 integrins was shown to inhibit neurite outgrowth

236 of two pathways (L-selectin and MAdCAM-1 or alpha4 integrins) was required to improve ileitis.

237 , T cells present in the CNS of mice lacking alpha4 integrin were mainly enriched in Th17 cells, sugg

238 sed transmigration times when both beta2 and alpha4 integrins were blocked.

239 Mice chimeric for the expression of alpha4 integrins were used to dissect the roles of these

240 same signaling properties as the full-length alpha4 integrin, whereas exchanging or removing cytoplas

241 positive/negative regulation in vivo is the alpha4 integrin, which play a key role in normal hematop

242 The alpha4 integrins, which are constitutively expressed on

243 Selectin-independent rolling was mediated by alpha4 integrins, which interacted with endothelial vasc

244 Blocking alpha4 integrin with a mAb increased rolling velocity to

245 Heterodimerization of the alpha4 integrin with endogenous beta1 integrin (CD29) wa

246 al mechanism to modulate paxillin binding to alpha4 integrins with consequent regulation of alpha4 in

247 alpha4 integrin mutant cells developing in [alpha4 integrin(-/-): wt] chimeric mice are not capable