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 n inflammatory sites are mediated in part by alpha4 integrins.

12 n flow and rolling interactions through both alpha4 integrins.

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

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

15 al killer cells can develop normally without alpha4 integrins.

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

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

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

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

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

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

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

23 The alpha4 integrin adhesion receptor is associated with enh

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

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

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

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

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

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

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

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

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

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

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

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

36 0.5 and 2.0 dynes/cm2 could be attributed to alpha4 integrin and VCAM-1.

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

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

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

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

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

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

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

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

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

46 Natalizumab is an alpha4 integrin antagonist that reduced the development

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

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

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

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

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

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

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

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

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

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

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

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

59 Alpha4 integrins are essential for definitive hematopoie

60 alpha4 integrins are essential for embryogenesis, hemato

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

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

63 alpha4 integrins are important mediators of leukocyte mi

64 The alpha4 integrins are indispensable for embryogenesis, ha

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

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

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

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

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

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

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

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

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

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

75 Furthermore, alpha4 integrin blockade reduced the trafficking of the

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

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

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

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

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

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

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

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

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

85 Alpha4 integrins contribute to the development of HFD-in

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

101 Anti-alpha4 integrin dramatically blocked the influx of MDSCs

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

128 Blocking alpha4 integrins interfered with the adhesion but not th

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

146 alpha4 integrin mutant cells developing in [alpha4 integ

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

162 1 integrin thus dominates beta7 integrin for alpha4 integrin pairing, thereby controlling the abundan

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

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

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

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

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

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

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

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

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

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

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

174 The alpha4 integrin protein, required for chorioallantoic fu

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

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

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

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

179 Such signals from alpha4 integrins regulate cell migration in development

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

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

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

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

184 Antagonists to alpha4 integrin show promise for several autoimmune and

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

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

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

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

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

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

191 -1, as well as a small molecule inhibitor of alpha4 integrins, significantly reduced sympathetic inne

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

193 The alpha4 integrin subunit that pairs with beta7 integrin c

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

195 1 represents a CSGAG binding site within the alpha4 integrin subunit.

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

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

198 2 in regulating the membrane organization of alpha4 integrin subunits.

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

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

201 /14-3-3-zeta interactions, and recently, the alpha4 integrin tail was reported to bind to 14-3-3-zeta

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

225 The alpha4 integrins, which are constitutively expressed on

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

227 Blocking alpha4 integrin with a mAb increased rolling velocity to

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

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

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