ライフサイエンスコーパス: VLA-4

1 integrins, principally via alpha(4)beta(1) (VLA-4).

2 d U937 cells expressing Very Late Antigen-4 (VLA-4).

3 4beta1 (also known as very late antigen-4 or VLA-4).

4 antigen 1 (LFA-1), and very late antigen 4 (VLA-4).

5 LFA-1 conformation in a manner analogous to VLA-4.

6 ariety of membrane proteins, one of which is VLA-4.

7 otential imaging candidate for overexpressed VLA-4.

8 and adhesion receptors, including CXCR4 and VLA-4.

9 mechanisms are involved in the regulation of VLA-4.

10 n MS pathogenesis and express high levels of VLA-4.

11 -I cells up-regulated expression of CD44 and VLA-4.

12 determined the affinity of the compounds for VLA-4.

13 the blood to sites of infection mediated by VLA-4.

14 zation and the signaling pathway of integrin VLA-4.

15 reased renal expression of LLT-1, MCP-1, and VLA-4.

16 abrogated using blocking antibodies against VLA-4.

17 cific CXCR4 inhibitor and antibodies against VLA-4.

18 (4)beta(7), or a monoclonal antibody against VLA-4 (19H8), significantly inhibited the TNF-alpha-indu

19 ese results suggest that treatment with anti-VLA-4 Ab has multiple effects on the immune system and m

20 We wanted to determine whether anti-VLA-4 Ab treatment affected the function and persistence

21 y not appreciated deleterious effect of anti-VLA-4 Ab treatment in combination with exposure to pertu

22 During T cell migration on VCAM-1, VLA-4 activation concurs with spatial redistribution of

23 This VLA-4 activation is mediated via a Rac1/Rap1 GTPase sign

24 ection fluorescence microscopy, we show that VLA-4 activation localizes to the lamellipodium in livin

25 e of HUTS-21 binding was also related to the VLA-4 activation state even at saturating ligand concent

26 agement of CD44 or of HCELL directly induces VLA-4 activation via G-protein-dependent signaling, trig

27 mechanism of CD11c/CD18 and very late Ag-4 (VLA-4) activation and cooperation in shear-resistant cel

28 Coblockade of LFA-1 and VLA-4 adhesion molecules temporarily depleted long-lived

29 onal CXCR4 and CXCR5 chemokine receptors and VLA-4 adhesion molecules.

30 signaling through neutrophil CXCR4 augments VLA-4 adhesion to VCAM-1 in vitro, an effect that is blo

31 igh-affinity CD11c, which directly activated VLA-4 adhesion via phosphorylated spleen tyrosine kinase

32 in turn activate multiple integrins (LFA-1, VLA-4), adhesion molecules (ICAM-1, MadCAM-1) and the ch

33 c are early and critical events in signaling VLA-4 adhesive function on foamy monocytes competent to

34 ement of hMSC HCELL with E-selectin triggers VLA-4 adhesiveness, resulting in shear-resistant adhesio

35 studies demonstrate that the timing of anti-VLA-4 administration can selectively affect pathologic p

36 ning small molecule that was used to monitor VLA-4 affinity changes in live cells.

37 thway that connects shear, Ca(2+) elevation, VLA-4 affinity, and cell avidity.

38 f adjacent thiols in the exofacial domain of VLA-4 after its ligation to stromal fibronectin.

39 VLA-4 (alpha(4)beta(1)) is a key integrin in the effecti

40 The integrin VLA-4 (alpha(4)beta(1)) mediates tethering and rolling e

41 Others have demonstrated that VLA-4 (alpha(4)beta(1)), a ligand for VCAM-1 or fibronec

42 We report that costimulation by the integrin VLA-4 (alpha4beta1) required SLP-76 domains implicated i

43 Very-late-antigen-4 (VLA-4, alpha4beta1 integrin, CD49d/CD29) is a transmembr

44 Increased expression of VLA-4 also resulted in increased transendothelial migrat

45 We also show that VEGFR1+ cells express VLA-4 (also known as integrin alpha4beta1), and that tum

46 ty peptidomimetic ligand for very late Ag-4 (VLA-4; also called integrin alpha4beta1) binding cells i

47 Very late antigen-4 (VLA-4; also called integrin alpha4beta1) is a transmembr

48 VCAM-1 is one of the main ligands of VLA-4, an integrin that is highly expressed on the surfa

49 rase 4 (PDE4) inhibitor, rolipram, with anti-VLA-4 and anti-IL-5 in a model of secondary allergen exp

50 In contrast, treatment with anti-VLA-4 and anti-IL-5 only prevented changes in RL and eos

51 okine receptors (CXCR4), adhesion molecules (VLA-4 and CD44), and hypoxia-related proteins.

52 n and ICAM-1 interactions as well as through VLA-4 and connecting segment-1 fibronectin/VCAM-1 intera

53 ch could be blocked using inhibitors against VLA-4 and CXCR4.

54 precursor cells (hGPs) were transfected with VLA-4 and labeled with superparamagnetic iron oxide that

55 through downregulation of adhesion molecules VLA-4 and LFA-1, which are necessary for macrophage migr

56 blocking alone, but was abrogated when both VLA-4 and MCAM were inhibited.

57 CLP was ICAM-1-dependent and independent of VLA-4 and VCAM-1.

58 s can be blocked in vivo by RGD peptides and VLA-4 and VLA-5 but not beta(2) blocking antibodies.

59 the presence of cytokines, the engagement of VLA-4 and VLA-5 integrins to the fibronectin fragment CH

60 ously shown that engagement of the integrins VLA-4 and VLA-5 to the fibronectin fragment CH-296 in co

61 es adhesive functions of T-cell alpha4beta1 (VLA-4) and alphaLbeta2 (LFA-1) in in vivo and in vitro m

62 Because alpha(4)beta(1) integrin (VLA-4) and its ligand VCAM-1 play a central role in the

63 e we show that the integrin alpha(4)beta(1) (VLA-4) and its ligand VCAM-1 were required, whereas the

64 Here we show that integrin alpha4beta1 (VLA-4) and VCAM-1 promote close intercellular adhesion b

65 -primed T cells express very late antigen-4 (VLA-4), and functional blocking antibodies to alpha4 cha

66 ion molecules (such as VCAM-1 the ligand for VLA-4), and leukocyte adhesion to vascular endothelium.

67 uding CXCR4, very late activation antigen 4 (VLA-4), and lymphocyte function-associated antigen 1.

68 M-1), CD49d (very late activating antigen-4, VLA-4), and/or MUC-1 on MM cell lines; as well as CD106

69 d these cells' relative expression of CXCR4, VLA-4, and LFA-1, the homing and adhesion molecules that

70 f adhesion between the alpha4beta1 integrin, VLA-4, and VCAM-1.

71 e higher level of very late antigen (VLA)-2, VLA-4, and VLA-5 on Sca-1(+)c-kit(+) cells from FL compa

72 alpha4beta1 (very late activation antigen-4 [VLA-4]) and vascular cell adhesion molecule-1 (VCAM-1) p

73 In contrast, HSPC mobilization by a VLA-4 antagonist was intact.

74 This increased retention can be blocked by a VLA-4 antagonist, suggesting that the cells retained aft

75 ed the ability of BIO 5192, a small-molecule VLA-4 antagonist, to regulate active proteolipid protein

76 In accord with reports that VLA-4 antagonists in vivo induce mobilization of hematop

77 acokinetic profiles typical of this class of VLA-4 antagonists, and sustained activity as measured by

78 Extremely potent very late antigen-4 (VLA-4) antagonists with picomolar, whole blood activity

79 Administration of IL-5 or VLA-4 antibody prior to OVA challenge prevented the deve

80 tly less in animals pretreated with the anti-VLA-4 antibody than in those receiving a control antibod

81 afor, a CXCR4 antagonist, and natalizumab, a VLA-4 antibody.

82 be developed by promoting the generation of VLA-4(+) antitumor Tc1 cells.

83 sts; 2) decrease ligand binding affinity for VLA-4 approximately 2 orders of magnitude; 3) exhibit an

84 activation of the alpha(4)beta(1) integrin, VLA-4) are slow to initiate in Lyn(-/-) BMMCs, but persi

85 ment of a pre-existing pool of high-affinity VLA-4 as previously thought.

86 Selective inhibition of the activated VLA-4 at the leading edge with a small molecule inhibito

87 igen (LFA-1) and VCAM-1/very late antigen-4 (VLA-4) at select time points compared with PBS-treated a

88 Here we show that interruption of the VCAM-1/VLA-4 axis with a small molecule inhibitor of VLA-4, BIO

89 rofoundly reduced cell surface expression of VLA-4 before and after stimulation.

90 onal antibodies HP1/2 and HP2/1, which block VLA-4 binding to both VCAM-1 and FN connecting segment-1

91 iently transfected with very late antigen-4 (VLA-4) binding to vascular cell adhesion molecule-1 (VCA

92 model system, changes in the affinity of the VLA-4-binding pocket were reflected in rapid cell aggreg

93 LA-4 axis with a small molecule inhibitor of VLA-4, BIO5192, results in a 30-fold increase in mobiliz

94 p-regulation of VLA-4 during EIU and suggest VLA-4 blockade as a promising therapeutic strategy for t

95 at lymphocyte trafficking into the CNS under VLA-4 blockade can occur by using the alternative adhesi

96 VLA-4 blockade in vivo significantly suppressed all uvei

97 ed rolling and residual adhesion, even under VLA-4 blockade.

98 Antibody to VLA-4 blocked the accumulation of peripheral tissue-deri

99 on of MCAM(+)/TH17 cells was not affected by VLA-4 blocking alone, but was abrogated when both VLA-4

100 CD13 and VLA-4 blocking and activating Abs were used in flow-base

101 se (hybridoma clone PS/2) is not specific to VLA-4 but inhibits both alpha4beta1 and alpha4beta7 inte

102 ansfection studies that CD44 associates with VLA-4 but not LFA-1 on the plasma membrane of immune cel

103 mokine receptor CXCR4 and the integrin dimer VLA-4, but lack expression of E-selectin ligands that pr

104 e conclude that conformational activation of VLA-4 by inside-out signaling is independent of and addi

105 icient to restrict CD8+ T cell expression of VLA-4 (by IL-4), thereby serving as a regulator for CD8+

106 ional blocking antibodies to alpha4 chain of VLA-4 (CD49d) inhibited the ability of MBP-primed T cell

107 cking of antibodies to the alpha(4) chain of VLA-4 (CD49d) suggest that VLA-4 integrin on MBP-primed

108 pha(4)beta(1)-integrin (very late antigen-4 (VLA-4), CD49d/CD29) is an adhesion receptor involved in

109 or leukocyte integrins, very late antigen-4 (VLA-4, CD49d/CD29).

110 xpression patterns of fibronectin and VEGFR1+VLA-4+ clusters dictate organ-specific tumour spread.

111 cell cycle and more cells express CXCR4 and VLA-4 compared with G-CSF-mobilized CD34(+) cells.

112 mice given antibodies against both CD18 and VLA-4 compared with mice given the anti-CD18 antibody an

113 suggesting that CD49d is solely expressed in VLA-4 complexes.

114 VLA-4 conformational activation has been associated with

115 of the leukocyte adhesion markers LFA-1 and VLA-4, consistent with its ability to improve leukocyte

116 This firm adhesion is also VLA-4 dependent, as shown by antibody inhibition.

117 neously migrate beneath MSCs in a CXCR4- and VLA-4-dependent fashion (pseudoemperipolesis).

118 ic lesions, KC but not murine MCP-1 triggers VLA-4-dependent monocyte recruitment.

119 , resulting in enhanced very late antigen-4 [VLA-4] directed adhesion and motility.

120 dependent adhesion, we showed that CXCR4 and VLA-4 directly interact in response to SDF-1, we further

121 vel evidence for functional up-regulation of VLA-4 during EIU and suggest VLA-4 blockade as a promisi

122 demonstrate unexpected synergism of CD44 and VLA-4 during lymphocyte extravasation.

123 the utility of small molecule inhibitors of VLA-4 either alone or in combination with G-CSF or AMD31

124 Preclinical administration of anti-VLA-4 either to naive recipients of primed encephalitoge

125 utant form Stat6 (Stat6VT) failed to express VLA-4 even in the absence of IL-4-stimulation.

126 s on the interaction of the alpha4 integrin (VLA-4) expressed on activated T cells with VCAM-1 expres

127 IL-18R/VEGF/VLA-4-expressing A375 and 1182 melanoma cells produced a

128 ative in vivo MR cell tracking revealed that VLA-4-expressing cells docked exclusively within the vas

129 d of the ipsilateral carotid artery and that VLA-4-expressing cells exhibited significantly enhanced

130 4-naive hGPs and LPS, and rats that received VLA-4-expressing hGPs and LPS.

131 but did not receive LPS, rats that received VLA-4-expressing hGPs but not LPS, rats that received VL

132 argeted intraarterial delivery and homing of VLA-4-expressing hGPs to inflamed endothelium is feasibl

133 and without the IL-18 receptor (IL-18R)/VEGF/VLA-4-expressing phenotype were identified, and their me

134 High VLA-4 expression (> median MFI), compared with low expre

135 erived from patient leukemic cells with high VLA-4 expression and activity, we demonstrated that AS10

136 Enhanced VLA-4 expression has been observed in multiple myeloma (

137 Dl-1, and BTLA expression; and (iv) reducing VLA-4 expression in both the T- and B-cell populations.

138 rted a direct effect of myeloma on increased VLA-4 expression in host hematopoietic microenvironmenta

139 results underscore the importance of B-cell VLA-4 expression in the pathogenesis of CNS autoimmunity

140 High VLA-4 expression is associated with better clinical outc

141 e show that IL-4-mediated down-regulation of VLA-4 expression is completely abrogated in Stat6-defici

142 , we report that the selective inhibition of VLA-4 expression on B cells impedes CNS accumulation of

143 Our recent studies have suggested that VLA-4 expression on CD8+ T cells is negatively controlle

144 VLA-4 expression on Tc2 cells was down-regulated in an i

145 suggesting that IL-4 uniquely down-regulates VLA-4 expression on these cells.

146 VLA-4 expression varied widely, with mean expression 60.

147 Multivariate analyses showed that low VLA-4 expression was an independent adverse prognostic f

148 patients with standard-risk AML, in whom low VLA-4 expression was associated with inferior DFS (34% +

149 In wild-type (WT) mice, VLA-4 expression was less on neutrophils that emigrated

150 alyses indicated that the prognostic role of VLA-4 expression was most prominent in patients with sta

151 However, antigen specificity and VLA-4 expression were required for more robust recruitme

152 ell motility in monocytes, alongside reduced VLA-4 expression, an integrin predominantly involved in

153 Patients with low VLA-4 expression, compared with high expression, had a h

154 nly the truncated form of CD44 together with VLA-4 fail to traffic to an inflamed site, thereby defin

155 esonance energy transfer analysis of a novel VLA-4 FRET sensor under total internal reflection fluore

156 uption of CXCR4 signaling and attenuation of VLA-4 function are independent mechanisms of mobilizatio

157 However, the antibody used to block VLA-4 function in the mouse (hybridoma clone PS/2) is no

158 b-mediated blockade of the adhesion molecule VLA-4 has been shown to ameliorate disease in human mult

159 h factor receptor-1 and very late antigen-4 (VLA-4) have been shown to arrive at sites of metastasis

160 +) T cells trafficking to CSF were uniformly VLA-4(high), LFA-1(high).

161 nd therapeutic potential comprised of TYRP2, VLA-4, HSP70, an HSP90 isoform and the MET oncoprotein.

162 the presence of costimulatory blockade, anti-VLA-4 impaired T-cell trafficking to the graft but not m

163 Interestingly, the blocking of VLA-4 impaired the ability of MBP-primed T cells to indu

164 P2A-Cy5 demonstrated binding specificity for VLA-4 in an immune-competent murine MM model.

165 ient transfection of SPIO-labeled cells with VLA-4 in combination with their arterial injection and t

166 s (P<0.05), suggesting an important role for VLA-4 in EIU.

167 ate that the CXCR4/SDF-1 axis interacts with VLA-4 in regulating migration and adhesion of WM cells i

168 This study illustrates a novel role of VLA-4 in regulating neuroantigen-primed T cell-induced a

169 we measured in real time affinity changes of VLA-4 in response to shear.

170 ely, these data support the critical role of VLA-4 in the effective intracranial tumor homing of adop

171 demonstrate that the affinity regulation of VLA-4 in the presence of shear was related to Ca(2+) sig

172 The counter-receptor for VLA-4 in this rat retina model appears to be fibronectin

173 Functional activation of VLA-4 in vivo was investigated in our previously introdu

174 the role of very late activation antigen 4 (VLA-4) in peripheral blood (PB) monocyte migration.

175 mRNA, the major endothelial cell ligand for VLA-4, increased more in E. coli than in S. pneumoniae p

176 uced by bacteria in the lungs occurs through VLA-4-independent mechanisms.

177 Similarly, CXCR4 or VLA-4 inhibition led to significant inhibition of adhesi

178 ncluding increased proliferation and loss of VLA-4 integrin expression because of down-regulation of

179 Our data suggest that VLA-4 integrin hybrid domain movement does not depend on

180 alpha(4) chain of VLA-4 (CD49d) suggest that VLA-4 integrin on MBP-primed T cells plays an important

181 ls with IFN-beta inhibited the expression of VLA-4 integrin on the surface of MBP-primed T cells and

182 Increased expression of CXCR4 and VLA-4 integrin resulted in concentration-dependent chemo

183 the affinity and conformational state of the VLA-4 integrin simultaneously with cell activation initi

184 Similar to VLA-4 integrin, modulation of the ligand dissociation ra

185 Both alpha4 and beta1, subunits of VLA-4 integrin, were found to be necessary for T cell co

186 Unlike selectins, VLA-4 integrin-mediated lymphocyte adhesiveness can be m

187 However, engagement of VLA-4 integrins on UCB-derived CD34(+) cells reduced cel

188 Although it is well-established that VCAM-1/VLA-4 interactions can play important roles in mediating

189 VLA-4 is a promising MM imaging and therapeutic biomarke

190 In this study, we show that VLA-4 is expressed on murine marrow neutrophils and decr

191 ta suggest that a subpopulation of activated VLA-4 is mainly localized to the leading edge of polariz

192 gest that beta1, but not alpha4, integrin of VLA-4 is the sex-specific molecule on T cell surface, an

193 We have shown that the integrin VLA-4 is used preferentially over LFA-1 in conjunction w

194 e demonstrate that the alpha4beta1 integrin (VLA-4) is the receptor that mediates CD47-stimulated SS

195 atalizumab, which binds very late antigen-4 (VLA-4), is a potent therapy for multiple sclerosis (MS).

196 molecule-1 (VCAM-1; CD106), the receptor for VLA-4, is an important mediator of adhesive and co-stimu

197 neal cavity after CLP, which is dependent on VLA-4, is impaired in above mutant and FcRgamma chain-de

198 nctional BM niche with hematopoietic CXCR4(+)VLA-4(+)LFA-1(+) nursery cells, which provide PC surviva

199 CD62L(-)) and expressing adhesion molecules (VLA-4(+)LFA-1(+)) complementary to activated brain endot

200 fic growth factors upregulate fibronectin--a VLA-4 ligand--in resident fibroblasts, providing a permi

201 Costimulatory VLA-4 ligands also prevented the centralization of SLP-7

202 VLA-4 ligation retarded these flows, even in the absence

203 e observed a high level of mortality in anti-VLA-4 mAb (PS/2)-treated mice with actively induced EAE

204 ple sclerosis patients treated with the anti-VLA-4 mAb natalizumab, which selectively inhibits cell m

205 CD20+ B cell depletion plus LFA-1/VLA-4 mAb treatment significantly prolonged Ag-specific

206 VLA-4 mean fluorescence intensity (MFI) varied 35-fold (

207 pha(4)beta(1) integrin, very late antigen-4 (VLA-4), measured with an LDV-containing small molecule,

208 teinase-9 secretion and very late antigen 4 (VLA-4)-mediated adhesion to vascular cell adhesion molec

209 uffles and showing increased very late Ag-4 (VLA-4)-mediated adhesion to VCAM-1-expressing target cel

210 olecule-1 (VCAM-1)- and very late antigen-4 (VLA-4)-mediated localization of CXCR4(+) megakaryocyte p

211 kinases control chemokine-induced LFA-1- and VLA-4-mediated adhesion as well as human T lymphocyte ho

212 -mediated adhesion of BMDM to ICAM-1 but not VLA-4-mediated adhesion to VCAM-1 was enhanced by Cbl-b

213 mma chain and Syk, leading to enhancement of VLA-4-mediated adhesion to VCAM-1.

214 perimental clinical agent, AS101, to degrade VLA-4-mediated chemoresistance and improve clinical resp

215 l cell-derived factor-1alpha (SDF-1alpha) on VLA-4-mediated lymphocyte adhesion, human PBL were flowe

216 s, showing that cross-talk between CXCR4 and VLA-4 modulates marrow retention of these cells.

217 Anti-VLA-4 monoclonal antibody (mAb) treatment prior to EAE o

218 rating that two adhesion molecules, CD44 and VLA-4, must be physically associated with each other on

219 gnificantly enhanced homing as compared with VLA-4-naive cells (1448 significant pixels+/-366.5 vs 11

220 helium significantly increased compared with VLA-4-naive control cells (71.5 cells per field of view+

221 ressing hGPs but not LPS, rats that received VLA-4-naive hGPs and LPS, and rats that received VLA-4-e

222 ting of three rats each): rats that received VLA-4-naive hGPs but did not receive LPS, rats that rece

223 dies that target the cell adhesion molecules VLA-4 (natalizumab; Tysabri for multiple sclerosis and C

224 ts under long-term anti-very late antigen-4 (VLA-4)/natalizumab therapy (LTNT) and from CNS specimens

225 ase in the percentage of nonapoptotic CD11b+ VLA-4-negative macrophages/monocytes in blood.

226 positive human melanoma B16F10 cells than in VLA-4-negative MDA-MB-231 cells (P < 0.05).

227 VLA-4-negative MDA-MB-231/firefly luciferase (fluc) huma

228 A-4-positive B16F10 mouse melanoma cells and VLA-4-negative MDA-MB-231/fluc human breast cancer tumor

229 = 7 and 8 mice) on nude mice implanted with VLA-4-negative MDA-MB-231/fluc human breast tumor cells

230 Interaction between the integrin VLA-4 on acute myelogenous leukemia (AML) cells with str

231 cordance with the differential expression of VLA-4 on Tc1 versus Tc2 cells, Tc1 cells alone were comp

232 d antigen-1 (LFA-1) and very late antigen-4 (VLA-4) on adhesion of influenza hemagglutinin (HA)-speci

233 The expression of very late antigen-4 (VLA-4) on the surface of MBP-primed T cells and inhibiti

234 Anti-very late antigen 4 (VLA-4; on neutrophils) inhibited adhesion to TNF-alpha-a

235 latory blockade was coupled with either anti-VLA-4 or anti-LFA-1.

236 pha(4)beta(1) integrin, very-late-antigen-4 (VLA-4 or CD49d).

237 However, blocking VLA-4 or vascular cell adhesion molecule 1 (VCAM-1) had

238 Blockade of alpha(4)beta(1) integrin (VLA-4) or vascular cell adhesion molecule-1, but not CD1

239 we evaluated 2 conjugates of a high-affinity VLA-4 peptidomimetic ligand, LLP2A, for PET/CT imaging i

240 64)Cu-CB-TE1A1P-PEG4-LLP2A), a high-affinity VLA-4 peptidomimetic-based radiopharmaceutical, was eval

241 anoma cells with and without the IL-18R/VEGF/VLA-4 phenotype had distinct transcript patterns.

242 m melanomas with and without the IL-18R/VEGF/VLA-4 phenotype may serve as diagnostic biomarkers of me

243 anoma cells with and without the IL-18R/VEGF/VLA-4 phenotype.

244 cells with, but not without, the IL-18R/VEGF/VLA-4 phenotype.

245 molecule 1 (VCAM-1) and very late antigen-4 (VLA-4) played an integral role in the activation of NF-k

246 VLA-4 plays a critical role in T cell trafficking into i

247 These data suggest that VLA-4 plays a small role in CD18-independent neutrophil

248 he antigen alpha4beta1 (very late antigen-4, VLA-4) plays an important role in the migration of white

249 ke of (64)Cu-CB-TE2A-LLP2A was determined in VLA-4-positive B16F10 mouse melanoma cells and VLA-4-neg

250 istribution experiments in nude mice bearing VLA-4-positive B16F10 subcutaneous tumors in the flank w

251 an breast tumor cells suggested an influx of VLA-4-positive BMD cells that corresponded to metastasis

252 re we describe experiments toward imaging of VLA-4-positive BMD cells using a high-affinity PET probe

253 d flow cytometry also showed upregulation of VLA-4-positive cell clusters and BMD cells at the metast

254 lank were conducted to validate targeting of VLA-4-positive cells in vivo.

255 Uptake of (64)Cu-CB-TE2A-LLP2A was higher in VLA-4-positive human melanoma B16F10 cells than in VLA-4

256 LLP2A-Cy5 demonstrated high specificity for VLA-4-positive mouse 5TGM1-GFP myeloma and nonmalignant

257 ng agents for melanoma and potentially other VLA-4-positive tumors.

258 unity, Nguyen et al. show that engagement of VLA-4 promotes sustained signaling by altering the dynam

259 Here we show that integrin alpha4beta1 (VLA-4) promotes the homing of circulating progenitor cel

260 CAM-1 depended on induction of high-affinity VLA-4 rather than recruitment of a pre-existing pool of

261 Although vascular cell adhesion molecule-1 (VLA-4 receptor) was expressed at all CNS barriers, P-sel

262 luidic adhesion assay was used for assessing VLA-4 receptor-mediated cell docking in vitro.

263 cule that preferentially binds high-affinity VLA-4 reduced PBL firm adhesion to VCAM-1 by 90%.

264 ens a range of therapeutic possibilities for VLA-4-related pathologies.

265 (64)Cu-CB-TE2A-LLP2A had high uptake in the VLA-4-rich organs marrow, spleen, and tumor (11.26% +/-

266 Here, we investigate VLA-4's role in endotoxin-induced uveitis (EIU).

267 nfected fibroblasts and express the integrin VLA-4, suggesting that the CTLs could cross endothelial

268 Secondly, VLA-4 synergizes with the B-cell receptor (BCR), providi

269 study demonstrated the potential of PET with VLA-4-targeted (64)Cu-CB-TE2A-LLP2A to visualize BMD cel

270 uce high-affinity conformations of LFA-1 and VLA-4 that recognize their endothelial cell ligands and

271 marrow is adhesion via very late antigen-4 (VLA-4), the alpha(4)beta(1) integrin heterodimer that bi

272 edly did not significantly affect binding of VLA-4 to its ligand VCAM-1 (vascular cell adhesion molec

273 the relationship of functional expression of VLA-4 to prognosis in AML, we studied marrow samples fro

274 We thus compared the ability of anti-VLA-4 to regulate proteolipid protein (PLP) 139-151-indu

275 Marrow neutrophils adhere via VLA-4 to VCAM-1, which is expressed on marrow endotheliu

276 Most significantly, anti-VLA-4 treatment either before or during ongoing R-EAE en

277 with anti-very late activation antigen (anti-VLA-4), uncovered potentially important insight in the i

278 y to probe the "switchblade-like" opening of VLA-4 upon activation.

279 onsistent with the half-life of low-affinity VLA-4-VCAM-1 bonds.

280 ate that the first step is rate limiting for VLA-4-VCAM-1 interactions.

281 en together, these results indicate that the VLA-4/VCAM adhesion pathway is critical in the retention

282 esults further demonstrate the complexity of VLA-4/VCAM interactions, particularly in a relapsing-rem

283 These results show that the VLA-4/VCAM-1 interaction during membrane antigen recogni

284 ransformed cells, and targeting NF-kappaB or VLA-4/VCAM-1 signaling could be a clinically relevant me

285 In a VLA-4/VCAM-1-specific myeloid cell adhesion model system

286 ymphocyte function-associated antigen-1) and VLA-4 (very late antigen-4) is essential for T-cell traf

287 P-1 (monocyte chemoattractant protein-1) and VLA-4 (very-late antigen-4).

288 rm adhesion due to blockage of high-affinity VLA-4 was paralleled by a 4-fold increase in the fractio

289 l of potency against the unactivated form of VLA-4 was shown to be sufficient to overcome the poor ph

290 ver, increased binding of soluble VCAM-1 via VLA-4 was significantly associated with longer OS, corre

291 ential costimulatory activity of intact anti-VLA-4, we examined the ability of BIO 5192, a small-mole

292 induced multiple states of high affinity of VLA-4, where the affinity change was accompanied by an e

293 h integrin beta1, forms very late antigen-4 (VLA-4), which interacts with vascular cell adhesion mole

294 mediated in part by the leukocyte integrin, VLA-4, which binds to endothelial vascular cell adhesion

295 s indicate [(64)Cu]-LLP2A is a PET probe for VLA-4, which when used in conjunction with [(18)F]-FDG,

296 ing P-selectin, interactions of the integrin VLA-4 with its ligand VCAM-1, and pertussis toxin-sensit

297 1 with its ligand ICAM-1 and of the integrin VLA-4 with its ligand VCAM-1, of polarized T cells at th

298 Interaction of very late antigen-4 (VLA-4) with its ligand vascular cell adhesion molecule-1

299 nd NODAGA-PEG4-LLP2A showed high affinity to VLA-4, with a comparable dissociation constant (0.28 vs.

300 g to infection expressed increased levels of VLA-4, with consequent improved entry into inflamed tiss