Characterization of a human lymphocyte surface sialoglycoprotein that is defective in Wiskott-Aldrich syndrome.

Remold‐O′Donnell, Eileen; Kenney, Dianne M.; Parkman, Robertson; Cairns, Lloyd; Savage, Beverley; Rosen, Fred S.

doi:10.1084/jem.159.6.1705

Cited by 189 publications

(18 citation statements)

References 47 publications

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“…Potential receptors for CD54 on the MkMPs are the leukocyte function-associated antigen 1 (LFA-1, CD11a/CD18), CD43 and macrophage-1 antigen (Mac-1, CD11b/CD18). The former two are expressed on Mks and platelets [47, 48], while Mac-1 is expressed at low level on Mks [49]. Mks and platelets also express CD54 [47], thus suggesting that binding of MkMPs to HSPCs could be also mediated by CD54 on MkMPs and its receptors LFA-1, Mac-1 and CD43 on CD34 + cells [50].…”

Section: Resultsmentioning

confidence: 99%

How do megakaryocytic microparticles target and deliver cargo to alter the fate of hematopoietic stem cells?

Jiang

Kao

Papoutsakis

2017

Journal of Controlled Release

122

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Megakaryocytic microparticles (MkMPs), the most abundant MPs in circulation, can induce the differentiation of hematopoietic stem and progenitor cells (HSPCs) into functional megakaryocytes. This MkMP capability could be explored for applications in transfusion medicine but also for delivery of nucleic acids and other molecules to HSPCs for targeted molecular therapy. Understanding how MkMPs target, deliver cargo and alter the fate of HSPCs is important for exploring such applications. We show that MkMPs, which are distinct from Mk exosomes (MkExos), target HSPCs with high specificity since they have no effect on other ontologically or physiologically related cells, namely mesenchymal stem cells, endothelial cells or granulocytes. The outcome is also specific: only cells of the megakaryocytic lineage are generated. Observation of intact fluorescently-tagged MkMPs inside HSPCs demonstrates endocytosis as one mechanism of cargo delivery. Fluorescent labeling and scanning electron microscopy (SEM) imaging show that direct fusion of MkMPs into HSPCs is also engaged in cargo delivery. SEM imaging detailed the membrane-fusion process in four stages leading to full adsorption of MkMPs into HSPCs. Specifically, macropinocytosis and lipid raft-mediated were shown here as mechanisms of MkMP uptake by HSPC. In contrast, the ontologically related platelet-derived MPs (PMPs) cannot be taken up by HSPCs although they bind to and induce HSPC aggregation. We show that platelet-like thrombin activation is apparently responsible for the different biological effects of MkMPs versus PMPs on HSPCs. We show that HSPC uropods are the preferential site for MkMP binding, and that CD54 (ICAM-1), CD11b, CD18 and CD43, localized on HSPC uropods, are involved in MkMP binding to HSPCs. Finally, we show that MkMP RNA is largely responsible for HSPC programming into Mk differentiation.

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Section: Resultsmentioning

confidence: 99%

How do megakaryocytic microparticles target and deliver cargo to alter the fate of hematopoietic stem cells?

Jiang

Kao

Papoutsakis

2017

Journal of Controlled Release

122

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“…It was of interest to study if CD43 could be used as marker to follow immunological status of graft patients. CD43 is known to be expressed on most hematologic cells except red blood cells [12, 13]. We demonstrated here that the number of antigenic sites recognized by the sialylo-dependent monoclonal antibody (L60) is about 4 times more elevated on monocytes than on lymphocytes in controls.…”

Section: Discussionmentioning

confidence: 52%

Comparative CD43 Behavior on Monocytes and Lymphocytes in Kidney Transplants

Jego

Sabri²,

Solèr³

et al. 2000

Nephron

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In human cultured monocytic cells stimulated by cytokines, CD43 was demonstrated to exhibit a modification of sialylated epitopes (dys-sialylation) [Soler et al: Leukoc Biol 1997;61:609–618]. Therefore, we chose to investigate CD43 behavior on patients who present pathological status implicating monocytes after renal graft (KTR). We performed flow cytometry after immune staining using monoclonal antibodies to CD43 sialic acid-dependent (L60) and -independent (L10) epitopes. Compared to normal controls, mean fluorescence intensity was never altered on lymphocytes. Conversely, on monocytes, we found different profiles with L60: 26% of patients having normal CD43 expression, 54% displayed decreased values and 20% had a double population of monocytes, the major one being normal and the minor one with a very low staining. Decreased values were more frequent among KTR during the first 3 months following transplantation. L10 immunostaining was not altered on monocytes in patients with low values of CD43 staining by L60, confirming that the mechanism involved was a CD43 dys-sialylation. We investigated a possible role of cyclosporin (CsA) on human monocytic (THP-1) and lymphoid (Jurkat) cell lines. CsA decreases CD43 expression in monocytic and not in lymphoid cell lines and could be responsible for the specific dys-sialylation of KTR monocytes. Whatever, CD43 dys-sialylation might lead to functional abnormalities of monocytes in KTR, possibly involving the adhesion process.

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“…For anti-CD43, anti-CD28 and/or anti-CD3 stimulation, cells were incubated 10 min on ice with either L10 (anti-CD43) [48], anti-CD28 (clone CD8.2), and/or OKT3 (anti-CD3ε) mAbs (4 µg/ml). Subsequently, primary Abs were crosslinked with the secondary Ab, RaMIg (4 µg/ml) [27], and cells were activated in a 37°C water-bath for specific times, after which cells were lysed as previously described [11].…”

Section: Methodsmentioning

confidence: 99%

Characterization of a novel interaction between transcription factor TFII‐I and the inducible tyrosine kinase in T cells

et al. 2009

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TCR signaling leads to the activation of kinases such as inducible tyrosine kinase (Itk), a key regulatory protein in T-lymphocyte activation and function. The homolog of Itk in B cells is Bruton's tyrosine kinase, previously shown to bind and phosphorylate the transcription factor TFII-I. TFII-I plays major roles in transcription and signaling. Our purpose herein was twofold: first, to identify some of the molecular determinants involved in TFII-I activation downstream of receptor crosslinking in T cells and second, to uncover the existence of Itk-TFII-I signaling in T lymphocytes. We report for the first time that TFII-I is tyrosine phosphorylated upon TCR, TCR/CD43, and TCR/CD28 co-receptor engagement in human and/or murine T cells. We show that Itk physically interacts with TFII-I and potentiates TFII-Idriven c-fos transcription. We demonstrate that TFII-I is phosphorylated upon co-expression of WT, but not kinase-dead, or kinase-dead/R29C mutant Itk, suggesting these residues are important for TFII-I phosphorylation, presumably via an Itk-dependent mechanism. Structural analysis of TFII-I-Itk interactions revealed that the first 90 residues of TFII-I are dispensable for Itk binding. Mutations within Itk's kinase, pleckstrin-homology, and prolinerich regions did not abolish TFII-I-Itk binding. Our results provide an initial step in understanding the biological role of Itk-TFII-I signaling in T-cell function.Key words: Co-stimulation . Inducible tyrosine kinase . T-cell receptors . T-cell signaling . Transcription factor TFII-I See accompanying commentary by AugustSupporting Information available online IntroductionT-lymphocyte activation through the TCR and other co-stimulatory molecules results in the initiation of downstream signaling cascades, which involve a vast array of protein kinases, phosphatases, adaptor molecules, and ultimately, transcription factors. The selectivity or redundancy of given signaling pathways demands a tight and co-ordinated spatio-temporal regulation in order to ensure proper T-cell function. One key regulatory enzyme that is activated upon TCR engagement is the hematopoietic non-receptor tyrosine kinase, inducible tyrosine kinase (Itk), a protein recognized for its 2584importance in T-lymphocyte development, activation, and function [1,2]. Itk is a member of the Tec family of kinases and is expressed in T cells, NKT cells, and mast cells [1,3]. Of the three members expressed in ab TCR 1 T cells (Itk, Rlk, and Tec), Itk exhibits the highest level of expression [1,3].The homolog of Itk in B cells is Bruton's tyrosine kinase (Btk), and contrary to what is known about Btk -where Btk mutations are responsible for the immunodeficiencies, X-linked agammaglobulinemia in humans [4,5] and X-linked immunodeficiency (Xid) in mice [6,7] -no naturally occurring mutations have been described for Itk. However, mice deficient in Itk have impaired thymic development, T-cell proliferation, cytokine production, and exhibit defects in T-cell activation processes downstream of the TCR [1,3].Previous...

show abstract

Characterization of a human lymphocyte surface sialoglycoprotein that is defective in Wiskott-Aldrich syndrome.

Cited by 189 publications

References 47 publications

How do megakaryocytic microparticles target and deliver cargo to alter the fate of hematopoietic stem cells?

How do megakaryocytic microparticles target and deliver cargo to alter the fate of hematopoietic stem cells?

Comparative CD43 Behavior on Monocytes and Lymphocytes in Kidney Transplants

Characterization of a novel interaction between transcription factor TFII‐I and the inducible tyrosine kinase in T cells

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