The alpha 4 integrin chain is a ligand for alpha 4 beta 7 and alpha 4 beta 1.

Altevogt, Peter; Hubbe, M; Ruppert, Michael; Lohr, Jens G.; Hoegen, Paul von; Sammar, Marei; Andrew, David P.; McEvoy, Leslie M.; Humphries, Martin J.; Butcher, EC

doi:10.1084/jem.182.2.345

Cited by 85 publications

(43 citation statements)

References 57 publications

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“…In addition to fibronectin, the matrix protein osteopontin can interact with the ␣ 4 integrin (47). In another study the ␣ 4 integrin could bind homotypically to the ␣ 4 integrin chain via a conserved LDV motif (48). Another possibility is that MAdCAM-1 could be the ligand for ␣ 4 integrin if the integrin is in a high affinity state (as appeared to be the case for neutrophils in our in vitro studies).…”

Section: Discussionmentioning

confidence: 97%

α4 Integrin-Dependent Leukocyte Recruitment Does Not Require VCAM-1 in a Chronic Model of Inflammation

Johnston

Chee

Issekutz

et al. 2000

The Journal of Immunology

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Rats immunized with Mycobacterium butyricum in Freund’s adjuvant develop a chronic vasculitis, with large increases in leukocyte rolling and adhesion in mesenteric postcapillary venules that are significantly inhibited with an α4 integrin Ab. Using intravital microscopy to visualize chronically inflamed microvessels, we demonstrated that α4 integrin-dependent leukocyte rolling and adhesion was inhibited with a β1 integrin, but not a β7 integrin Ab. To date, VCAM-1 has been presumed to be the primary ligand for α4β1 integrin in the vasculature. However, α4β1 integrin-dependent interactions were not reduced by monoclonal or polyclonal VCAM-1 Abs or a VCAM-1 antisense oligonucleotide despite increased VCAM-1 expression in the mesenteric vasculature. To ensure that the VCAM-1 Abs were functional and used at saturating concentrations, blood from Ab-treated rats was perfused over monolayers of CHO cells transfected with rat VCAM-1. Sufficient α4 integrin or VCAM-1 Ab was present to inhibit leukocyte interactions with rat VCAM-1 by 95–100%. Under in vitro flow conditions, only mononuclear leukocytes were recruited from blood of control rats onto purified VCAM-1. However, neutrophils were also recruited onto VCAM-1 from whole blood of adjuvant-immunized animals via α4 integrin. Another ligand for α4β1 integrin is the connecting segment-1 (CS-1) region of fibronectin. An Ab to the CS-1 portion of fibronectin, which did not reduce rolling and adhesion in adjuvant arthritis animals, completely inhibited leukocyte adhesion to CS-1 under static conditions. These findings provide the first evidence that α4β1 integrin-dependent leukocyte rolling and adhesion can occur in vivo via a mechanism other than VCAM-1.

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Section: Discussionmentioning

confidence: 97%

α4 Integrin-Dependent Leukocyte Recruitment Does Not Require VCAM-1 in a Chronic Model of Inflammation

Johnston

Chee

Issekutz

et al. 2000

The Journal of Immunology

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“…Integrin ␣4␤7 (LPAM-1) expressed in a subset of effector T cells or ␥␦T cells in the intestine 31,32 can mediate cell migration as a receptor for MAdCAM-1 and VCAM-1. [33][34][35] Therefore, the expression of integrin ␤7 in Nanog T cells BLOOD, 1 JULY 2007 ⅐ VOLUME 110, NUMBER 1 For personal use only. on May 12, 2018.…”

Section: Discussionmentioning

confidence: 99%

Forced expression of Nanog in hematopoietic stem cells results in a γδT-cell disorder

Tanaka¹,

Era²,

Nishikawa

et al. 2007

Blood

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Nanog is a key molecule involved in the maintenance of the self-renewal of undifferentiated embryonic stem (ES) cells. In this work we investigate whether Nanog can enhance self-renewal in hematopoietic stem cells. Contrary to our expectation, no positive effect of Nanog transduction was detected in bone marrow reconstitution assays. However, recipients of Nanog-transduced (Nanog) hematopoietic stem cells (HSCs) invariantly develop a unique disorder typified by an atrophic thymus occupied by Nanogexpressing ␥␦T-cell receptor-positive (TCR ؉ ) cells (Nanog T cells). All thymi are eventually occupied by Nanog T cells with CD25 ؉ CD44 ؉ surface phenotype that home selectively to the thymus on transfer and suppress normal thymocyte development, which is partly ascribed to destruction of the microenvironment in the thymus cortex. Moreover, this initial disorder invariantly develops to a lymphoproliferative disorder, in which Nanog T cells undergo unlimited proliferation in the peripheral lymphoid tissues and eventually kill the host. This invariable end result suggests that Nanog is a candidate oncogene for ␥␦T-cell IntroductionThe self-renewal capacity and multipotency of embryonic stem (ES) cells can easily be maintained in culture. Several molecules have been implicated in the maintenance of these essential features of ES cells. Oct3/4 in association with the high mobility group (HMG) factor Sox2 is reported to be essential for self-renewal of ES cells, 1-3 and forced Nanog expression can maintain the immature state of ES cells in a LIF-Stat3-independent manner. 4,5 However, the exact molecular mechanism underlying the maintenance of the stem cell state is yet to be elucidated.Several reports have suggested that the core factors maintaining ES self-renewal can affect the activity of other stem cells. For example, Oct3/4 is expressed in mesenchymal stem cells derived from CD133 ϩ cells in mobilized peripheral blood and cord blood. 6 Nanog was also shown to be expressed in circulating CD14 ϩ CD34 low endothelial cells. 7 Although the role of these molecules in adult tissue stem cells remains unclear, it has been expected that it may be possible to use them to enhance the self-renewal of tissue stem cells. This expectation is supported by the recent report of Hochedlinger et al 8 showing that Oct3/4 overexpression enhances the proliferation of tissue stem cells.Compared with ES cells, it has been difficult to maintain the self-renewal of unmanipulated hematopoietic stem cells in vitro, although forced expression of HoxB4 or activated ␤-catenin confers enhanced self-renewal to hematopoietic progenitor cells (HPCs) in vitro. 9,10 Hence, it is worthwhile to determine whether the molecules involved in the self-renewal of ES cells can enhance that of HPCs. The initial aim of this work was to evaluate the effect of ectopic expression of Nanog on the behavior of hematopoietic stem cells. Although this expectation was not the case, we report here that Nanog overexpression induces an unusual ␥␦T-cell receptor-positive (TCR...

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“…Potential mechanisms include increased costimulatory signals and/or overstabilization of normally low-affinity TCR-Ia interactions. Recently it was shown that CD49d itself can also act as a cellular ligand for both ␣ 4 ␤ 1 and ␣ 4 ␤ 7 , with functional consequences (44). Increased CD49d expression may therefore also provide an increased costimulatory signal to the adjacent CD49d transfectant cells.…”

Section: Discussionmentioning

confidence: 99%

CD49d Overexpression and T Cell Autoimmunity

Eisenbraun

Sonstein

et al. 2003

The Journal of Immunology

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D10.G4.1 (D10) cells, a murine conalbumin-reactive Th2 cell line, made to overexpress the β2 integrin LFA-1 by pharmacological manipulation or by transfection become autoreactive and are capable of inducing in vivo autoimmunity. However, whether this is specific to LFA-1 and whether overexpression of other T cell integrin molecules has the same effect are unknown. We examined the functional consequences of T cell CD49d (α4 integrin) overexpression by transfecting murine CD49d cDNA into D10 cells. Similar to the LFA-1-transfected cells, the CD49d-overexpressing T cells are autoreactive and proliferate in response to APCs in an MHC class II-dependent manner in the absence of nominal Ag. Additionally, CD49d overexpression is associated with increased in vitro adhesion to endothelial cells and increased in vivo splenic homing. However, in contrast to LFA-1 overexpression, increased T cell CD49d expression is not associated with autoreactive cytotoxicity or the ability to induce in vivo autoimmunity. In addition to the novel observation that CD49d overexpression is sufficient to induce T cell autoreactivity, our results also support the hypothesis that the ability to induce in vivo autoimmunity is related to T cell cytotoxicity and not to T cell proliferation function in the D10 murine adoptive transfer model of autoimmunity.

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The alpha 4 integrin chain is a ligand for alpha 4 beta 7 and alpha 4 beta 1.

Cited by 85 publications

References 57 publications

α4 Integrin-Dependent Leukocyte Recruitment Does Not Require VCAM-1 in a Chronic Model of Inflammation

α4 Integrin-Dependent Leukocyte Recruitment Does Not Require VCAM-1 in a Chronic Model of Inflammation

Forced expression of Nanog in hematopoietic stem cells results in a γδT-cell disorder

CD49d Overexpression and T Cell Autoimmunity

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