Alberto Anel

Universidad de Zaragoza

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Javier Naval

Universidad de Zaragoza

Isabel Marzo

Instituto de Investigación Sanitaria Aragón

Julián Pardo

Instituto de Investigación Sanitaria Aragón

Luis Martínez‐Lostao

Universidad de Zaragoza

Martín Villalba

Inserm

Andrés Piñeiro

Universidad de Lima

Diego de Miguel

Certe

Nacho Aguiló

Universidad de Zaragoza

Joaquín Marco-Brualla

Universidad de Zaragoza

Marı́a José Martı́nez-Lorenzo

Hospital Clínico Universitario Lozano Blesa

Cooperative Institutions

Inserm

245

Centre National de la Recherche Scientifique

194

Weatherford College

172

University of Michigan–Ann Arbor

166

Harvard University

147

Universidad de Zaragoza

127

National Institutes of Health

114

Chinese Academy of Sciences

104

Washtenaw Community College

104

Bernard (Czechia)

101

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Alpha‐fetoprotein‐mediated uptake of fatty acids by human T lymphocytes

Journal of Cellular Physiology (1992)

Juan María Torres Alberto Anel José Uriel

Abstract The binding to resting and activated T lymphocytes of two radiolabelled fatty acids (oleic and arachidonic) was studied in the presence or in the absence of alphafetoprotein (AFP) as carrier protein. Fatty acid binding by resting and activated T lymphocytes was determined at 4°C as a function of the concentration of fatty acid and AFP. Under the conditions employed, the following observations were made: (1) in the presence of AFP, fatty acids (oleic and arachidonic acid) are bound to cells by a two‐component pathway; one is a saturable process, evidenced when the fatty acid to AFP (FA/AFP) molar ratio was fixed at 1 and the concentration of the fatty acid and the protein varied from 0.1 to 3.2 μM, and the second is a nonsaturable function of FA/AFP molar ratio and was linearly related to the unbound fatty acid concentration in the medium over the entire range studied; (2) in the absence of AFP, the nonsaturable process appears to be the only component of fatty acid binding; (3) at all tested concentrations of free (unbound) fatty acid in the medium, net fatty acid binding by either resting or activated T cells was considerably greater in the presence than in the absence of AFP; (4) in the presence of AFP, fatty acid binding was much higher in activated T cells than in resting T cells, whereas in the absence of AFP, nonsignificant differences were observed between activated and resting T cells; and (5) the time course of fatty acid and AFP binding at 4°C revealed that, at equilibrium, the number of fatty acid molecules bound to the cell was much greater than that of AFP suggesting an accelerated dissociation of the fatty acid upon interaction of the AFP‐fatty acid complex with putative cell receptors. It is concluded to the existence of an AFP/AFP‐receptor pathway that facilitates the binding of fatty acids to T lymphocytes, particularly upon their blast transformation. This pathway may fulfill the increased requirement for fatty acids characteristic of proliferating cells and may serve to regulate the endocytosis of fatty acids with modulatory effects on lymphocyte function and to protect cells from their cytotoxic potential when internalized in excess.

10.1002/jcp.1041500305

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Citations (18)

Biosynthesis of unsaturated fatty acids in the main cell lineages of human leukemia and lymphoma

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism (1995)

Isabel Marzo Marı́a José Martı́nez-Lorenzo Alberto Anel Paula Desportes María A. Álava

Jurkat cells

Fatty acid desaturase

Stearoyl-CoA Desaturase

U937 cell

K562 cells

Unsaturated fatty acid

10.1016/0005-2760(95)00064-j

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Citations (35)

Granulysin-Induced Apoptosis. I. Involvement of at Least Two Distinct Pathways

The Journal of Immunology (1998)

Susana Gamen Dennis A. Hanson Allan Kaspar Javier Naval Alan M. Krensky

Granulysin is a newly described cytolytic molecule released by CTL and NK cells via granule-mediated exocytosis. It shares homology with saposin-like proteins, including NK-lysin and amoebapores, and has been implicated in the lysis of tumor cells and microbes. In the present study we show that recombinant granulysin alone induces apoptosis of Jurkat cells. This apoptosis is associated with a sixfold increase in the ceramide/sphingomyelin ratio, implicating the activation of sphingomyelinases. Granulysin- and ceramide-induced apoptosis are similar in that they both are only minimally inhibited by the more selective cysteine protease p32 (caspase 3)-like caspase inhibitor N-acetyl-Asp-Glu-Val-Asp aldehyde, while they are significantly inhibited by the more general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-fmk). Nevertheless, while Z-VAD-fmk almost completely inhibits ceramide-induced apoptosis, a Z-VAD-fmk-resistant component was observed using granulysin. Granulysin also causes apoptosis in cells depleted of sphingomyelin by prolonged treatment with the ceramide synthase inhibitor fumonisin B1. These data indicate that granulysin induces target cell death by both ceramide- and caspase-dependent and -independent pathways.

Granulysin

Jurkat cells

CD43

Granzyme

10.4049/jimmunol.161.4.1758

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Citations (133)

Interaction of rat α‐fetoprotein and albumin with polyunsaturated and other fatty acids: Determination of apparent association constants

FEBS Letters (1989)

Alberto Anel Miguel Calvo Javier Naval Marı́a Iturralde María A. Álava

The interaction of fatty acids with rat α‐fetoprotein and albumin was measured using a partition equilibrium method. α‐Fetoprotein (AFP) displays one high‐affinity binding site for fatty acids and albumin near two binding sites. The AFP association constants for most fatty acids were similar to those of albumin (in the 10 7 M −1 range) whereas for docosa‐hexaenoic acid it was 9.7 × 10 8 M −1 , about 50‐fold higher than that corresponding to albumin. This difference justifies docosahexaenoic acid in fetal or neonatal serum being mainly bound to AFP and can indicate a highly specific role of AFP in the transport of this fatty acid.

10.1016/0014-5793(89)80676-3

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Citations (22)

Liposomes Decorated with Apo2L/TRAIL Overcome Chemoresistance of Human Hematologic Tumor Cells

Molecular Pharmaceutics (2013)

Diego de Miguel Gorka Basáñez Diego Sánchez‐Martínez Patricia Galán-Malo Isabel Marzo

Human Apo2-ligand/TRAIL is a member of the TNF cytokine superfamily capable of inducing apoptosis on tumor cells while sparing normal cells. Besides its antitumor activity, Apo2L/TRAIL is also implicated in immune regulation. Apo2L/TRAIL is stored inside activated T cells in cytoplasmic multivesicular bodies and is physiologically released to the extracellular medium inserted in the internal membrane vesicles, known as exosomes. In this study we have generated artificial lipid vesicles coated with bioactive Apo2L/TRAIL, which resemble natural exosomes, to analyze their apoptosis-inducing ability on cell lines from hematological tumors. We have tethered Apo2L/TRAIL to lipid vesicles by using a novel Ni(2+)-(N-5-amino-1-carboxylpentyl)-iminodiacetic acid, NTA)-containing liposomal system. This lipidic framework (LUVs-Apo2L/TRAIL) greatly improves Apo2L/TRAIL activity, decreasing by around 14-fold the LC50 on the T-cell leukemia Jurkat. This increase in bioactivity correlated with the greater ability of LUVs-Apo2L/TRAIL to induce caspase-3 activation and is probably due to the increase in local concentration of Apo2L/TRAIL, improving its receptor cross-linking efficiency. More important, liposome-bound Apo2L/TRAIL overcame the resistance to soluble recombinant Apo2L/TRAIL exhibited by tumor cell mutants overexpressing Bcl-xL or by a Bax and Bak-defective Jurkat cell mutant (Jurkat-shBak) and are also effective against other hematologic tumor cells. Jurkat-Bcl-xL and Jurkat-shBak cells are resistant to most chemotherapeutic drugs currently used in cancer treatment, and their sensitivity to LUVs-Apo2L/TRAIL could have potential clinical applications.

Jurkat cells

10.1021/mp300258c

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Citations (77)

Characterization of the lipolytic pathways that mediate free fatty acid release during Fas/CD95-induced apoptosis

APOPTOSIS (2005)

Marı́a Iturralde Julián Pardo Esther Lacasa Gloria del Barrio M.A. Álava

10.1007/s10495-005-1511-1

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Citations (5)

The differential contribution of granzyme A and granzyme B in cytotoxic T lymphocyte-mediated apoptosis is determined by the quality of target cells

European Journal of Immunology (2002)

Julián Pardo Sandra Balkow Alberto Anel Markus M. Simon

Complementary approaches with purified molecules or transfected cytolytic effector cells have suggested that both, granzyme A (gzmA) and granzyme B (gzmB), similarly contribute to CTL-mediatedand perforin (perf)-dependent apoptotic nuclear damage (DNA fragmentation) in target cells. Studies employing gzmA or gzmB single-knockout mice on the other hand indicated that gzmB is the prominent CTL effector molecule for the rapid induction of DNA fragmentation, with gzmA playing only a minor part. We have now taken ex vivo-derived virus-specific or in vitro generated alloreactive CTL from mice deficient in either gzmA or gzmB and a panel of three target cells to reinvestigate this unresolved issue. We show that rapid CTL-mediated DNA fragmentation of L1210.3 target cells is solely dependent on gzmB, whereas the DNA fragmentation of EL4.F15 target cells by the same CTL population is mainly induced by gzmA and only marginally by gzmB. Moreover, CTL-induced apoptosis of a third target cell, MC57G, was partially dependent on both gzmA and gzmB activities. The differential contribution of the two gzms to apoptosis was further verified by their distinct sensitivity tocaspase inhibitors. The data suggest that both, gzmA and gzmB, have a similar potential to induce rapid perf-mediated apoptosis but that their individual contribution to the underlying intracellular processes is dictated by the quality of the target cell.

CTL*

Granzyme A

Granzyme

10.1002/1521-4141(200207)32:7<1980::aid-immu1980>3.0.co;2-z

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Citations (63)

Membrane partition of fatty acids and inhibition of T cell function

Biochemistry (1993)

Alberto Anel Gary V. Richieri Alan M. Kleinfeld

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMembrane partition of fatty acids and inhibition of T cell functionAlberto Anel, Gary V. Richieri, and Alan M. KleinfeldCite this: Biochemistry 1993, 32, 2, 530–536Publication Date (Print):January 19, 1993Publication History Published online1 May 2002Published inissue 19 January 1993https://pubs.acs.org/doi/10.1021/bi00053a018https://doi.org/10.1021/bi00053a018research-articleACS PublicationsRequest reuse permissionsArticle Views254Altmetric-Citations90LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

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10.1021/bi00053a018

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Citations (117)

Ecto-calreticulin expression in multiple myeloma correlates with a failed anti-tumoral immune response and bad prognosis

OncoImmunology (2022)

Alfonso Serrano del Valle Manuel Beltrán‐Visiedo Victoria de Poo-Rodríguez Nelia Jiménez‐Alduán Gemma Azaceta

Immunogenic cell death (ICD) has been proposed to be a crucial process for antitumor immunosurveillance. ICD is characterized by the exposure and emission of Damage Associated Molecular Patterns (DAMP), including calreticulin (CRT). A positive correlation between CRT exposure or total expression and improved anticancer immunosurveillance has been found in certain cancers, usually accompanied by favorable patient prognosis. In the present study, we sought to evaluate CRT levels in the plasma membrane of CD38+ bone marrow mononuclear cells (BMMCs) isolated from 71 patients with varying degrees of multiple myeloma (MM) disease and examine the possible relationship between basal CRT exposure and the bone marrow immune microenvironment, as well as its connection with different clinical markers. Data show that increased levels of cell surface-CRT were associated with more aggressive clinical features and with worse clinical prognosis in MM. High CRT expression in MM cells was associated with increased infiltration of NK cells, CD8+ T lymphocytes and dendritic cells (DC), indicative of an active anti-tumoral immune response, but also with a significantly higher presence of immunosuppressive Treg cells and increased expression of PD-L1 in myeloma cells.

Immunosurveillance

Immunogenic cell death

10.1080/2162402x.2022.2141973

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Citations (7)

The induction of Bim expression in human T-cell blasts is dependent on nonapoptotic Fas/CD95 signaling

Blood (2006)

Alberto Bosque Nacho Aguiló M.A. Álava Estela Paz‐Artal Javier Naval

Fas ligand

Autoimmune lymphoproliferative syndrome

Jurkat cells

10.1182/blood-2006-05-022319

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Citations (24)