Association between biomechanical alterations and migratory ability of semaphorin-3A-treated thymocytes

Lins, Marvin Paulo; Silva, Elaine Cristina Oliveira da; Silva, Givanildo Rodrigues da; Souza, Samuel T.; Medeiros, Návylla Candeia de; Fonseca, E. J. S.; Smaniotto, Salete

doi:10.1016/j.bbagen.2018.01.001

Cited by 10 publications

(7 citation statements)

References 65 publications

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“…Besides migration, semaphorin 3A also aff ects cell adhesion and cell-cell cooperation in the immune system. It suppresses mouse thymocyte [80] and CD8 + T cell [21] adhesion to extracellular matrix, contact formation between thymocytes and thymic epithelial cells [54], as well as between DCs and T cells [20]. Moreover, semaphorin 3A inhibits interaction of T lymphocytes with tumor cells, namely T cell adhesion to them [13] and cytotoxic activity [41].…”

Section: Discussionmentioning

confidence: 99%

Semaphorin 3A in the Immune System: Twenty Years of Study

Kiseleva

Rutto

2022

Biochemistry Moscow

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Semaphorin 3A is a secreted glycoprotein, which was originally identifi ed as axon guidance factor in the neuronal system, but it also possesses immunoregulatory properties. Here, the eff ect of semaphorin 3A on T-lymphocytes, myeloid dendritic cells and macrophages is systematically analyzed on the bases of all publications available in the literature for 20 years. Expression of semaphorin 3A receptors -neuropilin-1 and plexins A -in these cells is described in details. The data obtained on human and murine cells is described comparatively. A comprehensive overview of the interaction of semaphorin 3A with mononuclear phagocyte system is presented for the fi rst time. Semaphorin 3A signaling mostly results in changes of the cytoskeletal machinery and cellular morphology that regulate pathways involved in migration, adhesion, and cell-cell cooperation of immune cells. Accumulating evidence indicates that this factor is crucially involved in various phases of immune responses, including initiation phase, antigen presentation, eff ector T cell function, infl ammation phase, macrophage activation, and polarization. In recent years, interest in this fi eld has increased signifi cantly because semaphorin 3A is associated with many human diseases and therefore can be used as a target for their treatment. Its involvement in the immune responses is important to study, because semaphorin 3A and its receptors turn to be a promising new therapeutic tools to be applied in many autoimmune, allergic, and oncology diseases.

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Section: Discussionmentioning

confidence: 99%

Semaphorin 3A in the Immune System: Twenty Years of Study

Kiseleva

Rutto

2022

Biochemistry Moscow

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“…Cell mechanics is gaining traction as an important biomarker of cell differentiation, pathophysiology, and cancer progression (Li et al 2008;Liang et al 2016;Liu et al 2015;Qiu et al 2010). The biomechanics of various cell types has been explored using optical tweezers, micropipette aspiration, magnetic twisting cytometry, and atomic force microscopy (AFM), among others (Lins et al 2018;Pillarisetti et al 2011;Yim et al 2010;Yokokawa et al 2008). The utility of AFM to study the mechanical properties of individual cells under pathological and toxicant-aberrant conditions is gaining attention (Angely et al 2017;Gavara and Chadwick 2012;Kim et al 2012;Pastrana et al 2019).…”

Section: Introductionmentioning

confidence: 99%

Biophysical and biomechanical properties of neural progenitor cells as indicators of developmental neurotoxicity

2019

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Conventional in vitro toxicity studies have focused on identifying IC 50 and the underlying mechanisms, but how toxicants influence biophysical and biomechanical changes in human cells, especially during developmental stages, remain under-studied. Here, using an atomic force microscope, we characterized changes in biophysical (cell area, actin organization) and biomechanical (Young's modulus, force of adhesion, tether force, membrane tension, tether radius) aspects of human fetal brain-derived neural progenitor cells (NPCs) induced by four classes of widely used toxic compounds, including rotenone, digoxin, N-arachidonoylethanolamide (AEA), and chlorpyrifos, under exposure up to 36 h. The sub-cellular mechanisms (apoptosis, mitochondria membrane potential, DNA damage, glutathione levels) by which these toxicants induced biochemical changes in NPCs were assessed. Results suggest a significant compromise in cell viability with increasing toxicant concentration (p < 0.01), and biophysical and biomechanical characteristics with increasing exposure time (p < 0.01) as well as toxicant concentration (p < 0.01). Impairment of mitochondrial membrane potential appears to be the most sensitive mechanism of neurotoxicity for rotenone, AEA and chlorpyrifos exposure, but compromise in plasma membrane integrity for digoxin exposure. The surviving NPCs remarkably retained stemness (SOX2 expression) even at high toxicant concentrations. A negative linear correlation (R 2 = 0.92) exists between the elastic modulus of surviving cells and the number of living cells in that environment. We propose that even subtle compromise in cell mechanics could serve as a crucial marker of developmental neurotoxicity (mechanotoxicology) and therefore should be included as part of toxicology assessment repertoire to characterize as well as predict developmental outcomes.

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“…После этого исследователи впервые обратили внимание на то, что кроме хемоаттракции существует также и хеморепелленция клеток иммунной системы. Если миграцию тимоцитов индуцировали с помощью хемокина SDF-1, семафорин 3А оказывал ингибирующий эффект [7], снижая экспрессию рецептора CXCR4 в мигрирующих клетках [4]. В отношении адгезии семафорин 3А также оказывал негативное действие, подавляя адгезию тимоцитов человека к эпителиальным клеткам тимуса [6] и тимоцитов мыши к субстрату [7].…”

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“…Если миграцию тимоцитов индуцировали с помощью хемокина SDF-1, семафорин 3А оказывал ингибирующий эффект [7], снижая экспрессию рецептора CXCR4 в мигрирующих клетках [4]. В отношении адгезии семафорин 3А также оказывал негативное действие, подавляя адгезию тимоцитов человека к эпителиальным клеткам тимуса [6] и тимоцитов мыши к субстрату [7]. При этом семафорин 3A оказывал влияние на цитоскелет, индуцируя образование филоподий и накопление фибриллярного актина в наружном слое цитоплазмы тимоцитов [7].…”

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“…В отношении адгезии семафорин 3А также оказывал негативное действие, подавляя адгезию тимоцитов человека к эпителиальным клеткам тимуса [6] и тимоцитов мыши к субстрату [7]. При этом семафорин 3A оказывал влияние на цитоскелет, индуцируя образование филоподий и накопление фибриллярного актина в наружном слое цитоплазмы тимоцитов [7].…”

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Semaphorin 3a - A New Intrathymic Suppressor Factor

Rutto

Kisseleva

Kiseleva³

2019

Medical academic journal

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Semaphorins were originally identified as axon guidance factors involved in the development of the neuronal system. However, accumulating evidence indicates that several semaphorins, so-called ‘immune semaphorins’, are also involved in various phases of immune responses. One of such factors is semaphorin 3A - a member of class 3 semaphorins, which are secretory molecules in vertebrates. There are multiple mechanisms involved in the process of semaphorin 3A-mediated regulation. One of them is down-regulation of peripheral T-cell activity in consequence of which semaphorin 3A is considered as an immunosuppressive factor. But semaphorin 3A is also expressed in the thymus while its function there remains obscure. Here are discussed new data on immunosuppressive function of this factor towards thymocytes and thymic epithelial cells, obtained in vitro. Because it is involved both in physiological immunoregulation and in the pathogenesis of many autoimmune, atopic, and malignant diseases, semaphorin 3A turns to be a promising therapeutic tool to be studied and applied in these diseases.

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Association between biomechanical alterations and migratory ability of semaphorin-3A-treated thymocytes

Cited by 10 publications

References 65 publications

Semaphorin 3A in the Immune System: Twenty Years of Study

Semaphorin 3A in the Immune System: Twenty Years of Study

Biophysical and biomechanical properties of neural progenitor cells as indicators of developmental neurotoxicity

Semaphorin 3a - A New Intrathymic Suppressor Factor

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