A5047016562- Cell Adhesion Molecules Research
- Lymphoma Diagnosis and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Sarcoma Diagnosis and Treatment
- Platelet Disorders and Treatments
- Ubiquitin and proteasome pathways
- Signaling Pathways in Disease
- Immune Response and Inflammation
- Connective tissue disorders research
- T-cell and B-cell Immunology
- Mitochondrial Function and Pathology
- Cancer-related Molecular Pathways
- Immunotherapy and Immune Responses
- Viral-associated cancers and disorders
- Biochemical and Structural Characterization
- Aortic aneurysm repair treatments
- Epigenetics and DNA Methylation
- Protease and Inhibitor Mechanisms
- Glycosylation and Glycoproteins Research
- Galectins and Cancer Biology
- Ocular Oncology and Treatments
- Aortic Disease and Treatment Approaches
- Cancer Cells and Metastasis
- Macrophage Migration Inhibitory Factor
- Immune cells in cancer
Universidad Autónoma de Madrid
2013-2025
Consejo Superior de Investigaciones Científicas
2007-2025
Centro de Investigación en Red en Enfermedades Cardiovasculares
2017-2025
Centro de Investigación Biomédica en Red
2019-2025
Centro de Biología Molecular Severo Ochoa
2021-2025
Instituto de Salud Carlos III
2023-2025
National Research Council
2024
Hospital Universitario La Paz
2023
Hospital La Paz Institute for Health Research
2023
Instituto de Investigaciones en Ciencias de la Salud
2023
The human integrin VLA (very late activation antigens)-4 (CD49d/CD29), the leukocyte receptor for both CS-1 region of plasma fibronectin (Fn) and vascular cell surface adhesion molecule-1 (VCAM-1), also mediates homotypic aggregation upon triggering with specific anti-VLA-4 monoclonal antibody (mAb). Epitope mapping this on B-cell line Ramos, performed a wide panel mAb by cross-competitive binding protease sensitivity assays, revealed existence three topographically distinct epitopes alpha 4...
Regulation of gene expression in mammals through methylation cytosine residues at CpG dinucleotides is involved the development and progression tumors. Because many genes that are control cell proliferation regulated by members E2F family transcription factors because some DNA-binding sites methylated vivo , we have investigated whether can regulate functions. We show here elements derived from dihydrofolate reductase, E2F1, cdc2 promoters prevents binding all tested (E2F1 E2F5). In...
Integrins from the very late activation antigen (VLA) subfamily are involved in cellular attachment to extracellular matrix (ECM) proteins and intercellular adhesions. It is known that interaction of integrin with their ligands can be regulated during activation. We have investigated regulation different VLA-mediated adhesive interactions through common beta 1 chain. found certain anti-beta antibodies strongly enhance binding myelomonocytic U-937 cells fibronectin. This 1-mediated regulatory...
Cyclin G2 is an unconventional cyclin highly expressed in postmitotic cells. Unlike classical cyclins that promote cell cycle progression, blocks entry. Here we studied the mechanisms regulate mRNA expression during cycle. Analysis of synchronized NIH 3T3 cultures showed elevated levels at G(0), with a considerable reduction as cells enter Downregulation requires activation phosphoinositide 3-kinase, suggesting this enzyme controls expression. Because 3-kinase pathway inhibits FoxO family...
The E2F family of transcription factors plays a key role in regulating cell-cycle progression. Accordingly, is itself tightly controlled by series transcriptional and posttranscriptional events. Here we provide evidence that E2F1 protein levels are regulated the ubiquitin–proteasome-dependent degradation pathway. An analysis mutants identified conserved carboxyl-terminal region, which required for eliciting ubiquitination turnover. Fusion this sequence to heterologous protein, GAL4, resulted...
The VLA-4 (CD49d/CD29) integrin is the only member of VLA family expressed by resting lymphoid cells that has been involved in cell-cell adhesive interactions. We here describe triggering homotypic cell aggregation peripheral blood T lymphocytes and myelomonocytic mAbs specific for certain epitopes human alpha 4 subunit. This anti-VLA-4-induced adhesion isotype Fc independent. Similar to phorbol ester-induced adhesion, triggered through requires presence divalent cations, integrity...
The interaction of lymphocyte function-associated antigen-1 (LFA-1) with its ligands mediates multiple cell adhesion processes capital importance during immune responses. We have obtained three anti-ICAM-3 mAbs which recognize two different epitopes (A and B) on the intercellular molecule-3 (ICAM-3) as demonstrated by sequential immunoprecipitation cross-competitive mAb-binding experiments. Immunoaffinity purified ICAM-3-coated surfaces were able to support T lymphoblast attachment upon...
The activation of the endothelial cells by extravascular stimuli is key event in extravasation circulating leukocytes to target tissues. L-selectin, a member selectin family, constitutively expressed white cells, and molecule involved initial binding activated endothelium. After activation, rapidly release L-selectin from cell surface, suggesting that functional activity this controlled large part its appearance disappearance surface. We have studied neutrophil-activated assay, effect...
Abstract Adhesion of human neutrophils to endothelial cells is a crucial step during migration the extravascular sites inflammation. A large number molecules, including CD44 and LAM‐1 antigens, have been described participate in this process. We investigated regulation by recombinant tumor necrosis factor‐α (TNF‐α) neutrophil plasma membrane expression both adhesion as well that CD43 sialophorin, which has involved activation leukocytes. The these three antigens was down‐regulated upon TNF‐α...
Thoracic aortic aneurysm, as occurs in Marfan syndrome, is generally asymptomatic until dissection or rupture, requiring surgical intervention the only available treatment. Here, we show that nitric oxide (NO) signaling dysregulates actin cytoskeleton dynamics Syndrome smooth muscle cells and NO-donors induce Marfan-like aortopathy wild-type mice, indicating a marked increase NO suffices to aortopathy. Levels of nitrated proteins are higher plasma from patients mice tissue than control...
Abstract Optimal activation of human T cells mediated by ligation CD3/T cell receptor (TcR) complex requires co‐stimulatory signals. These can be provided the adhesive interaction between molecules on and their counter‐receptors antigen‐presenting cells. Soluble ICAM‐3, anti‐ICAM‐3 anti‐CD3 mAb were utilized to address role ICAM‐3/LFA‐1 pathway in TcR/CD3‐dependent or ‐independent activation. Immunoaffinity‐purified ICAM‐3 co‐immobilized with suboptimal concentrations monoclonal antibody...
Intercellular adhesion molecule (ICAM)-3, a recently described counter-receptor for the lymphocyte function-associated antigen (LFA)-1 integrin, appears to play an important role in initial phase of immune response. We have previously involvement ICAM-3 regulation LFA-1/ICAM-1-dependent cell-cell interaction T lymphoblasts. In this study, we further investigated functional other leukocyte interactions as well molecular mechanisms regulating these processes. found that is also able mediate...
Abstract Human activation inducer molecule (AIM/CD69), a dimeric glycoprotein of 33 and 27 kDa, is the earliest inducible cell surface antigen expressed during lymphocyte activation, which has been also involved in proliferation. Although AIM absent from peripheral blood resting lymphocytes, it by vivo activated lymphocytes infiltrating sites chronic inflammation several pathologies, as well after vitro with different stimuli. We have investigated possibility that tumor necrosis factor‐α...
Artery wall remodeling, a major feature of diseases such as hypertension, restenosis, atherosclerosis, and aneurysm, involves changes in the tunica media mass that reduce or increase vessel lumen. The identification molecules involved remodeling could aid development improved treatments for these pathologies. Angiotensin II (AngII) is key effector aortic contributes to aneurysm formation restenosis through incompletely defined signaling pathways. We show AngII induces vascular smooth muscle...
Abstract Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening condition associated with Marfan syndrome (MFS), disease caused by fibrillin-1 gene mutations. While various conditions causing TAAD exhibit accumulation of the proteoglycans versican (Vcan) aggrecan (Acan), it unclear whether these ECM proteins are involved in disease. Here, we find that Vcan, but not Acan, accumulated Fbn1 C1041G/+ aortas, mouse model MFS. Vcan haploinsufficiency protected MFS mice against...
Leukocyte activation is a complex process that involves multiple cross-regulated cell adhesion events. In this report, we investigated the role of intercellular molecule-3 (ICAM-3), third identified ligand for beta 2 integrin leukocyte function-associated antigen-1 (LFA-1), in regulation to ICAM-1, vascular molecule-1 (VCAM-1), and 38- 80-kD fragments fibronectin (FN40 FN80). The activating anti-ICAM-3 HP2/19, but not other mAb, was able enhance T lymphoblast these proteins when combined...
The myelodysplastic/myeloproliferative diseases (MDS/MPDs) are a heterogeneous group of myeloid neoplasms that share characteristics with chronic myeloproliferative and myelodysplastic syndromes. broad spectrum clinical manifestations makes MDS/MPDs extremely difficult to diagnose treat, median survival time 1-5 years. No single gene defect has been firmly associated MDS/MPDs, no animal models have developed for these diseases. association deletions on chromosome 20q malignancies suggests...
Whereas all of the integrins in VLA protein subfamily are involved cell-extracellular matrix interactions, only VLA-4 (through alpha 4 subunit) has been implicated triggering intercellular adhesion. Here we describe that beta 1 subunit (CD29) is also induction homotypic cell aggregation. We have obtained three novel anti-beta monoclonal antibodies (mAb) with ability to induce aggregation on different leukocyte types. These mAb recognize an antigenic site common chain proteins which...
Abstract Current treatments of sporadic Burkitt's lymphoma (sBL) are associated with severe toxicities. A better understanding sBL formation would facilitate development less toxic therapies. The etiology remains, however, largely unknown, C-MYC up-regulation being the only lesion known to occur in all cases. Several studies examining role pathogenesis BL have concluded that translocation is not critical event and additional unidentified factors expected be involved this tumor. We herein...
c-Myc, a member of the Myc family transcription factors, is involved in numerous biological functions including regulation cell proliferation, differentiation, and apoptosis various types. Of all its functions, role c-Myc differentiation one least understood. We addressed B lymphocyte differentiation. found that essential from early stages vivo regulates this process by providing identity via direct transcriptional ebf-1 gene. Our data show influences promoting activation genes, thus linking...
Failures in neurotrophic support and signalling play key roles Alzheimer's disease (AD) pathogenesis. We previously demonstrated that downregulation of the neurotrophin effector Kinase D interacting substrate (Kidins220) by excitotoxicity cerebral ischaemia contributed to neuronal death. This downregulation, triggered through overactivation N-methyl-d-aspartate receptors (NMDARs), involved proteolysis Kidins220 calpain transcriptional inhibition. As is at basis AD aetiology, we hypothesized...