Shear Stress Induces a Time-Dependent Inflammatory Response in Human Monocyte-Derived Macrophages.

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Title: Shear Stress Induces a Time-Dependent Inflammatory Response in Human Monocyte-Derived Macrophages.
Authors: Jui, Elysa1 (AUTHOR), Kingsley, Griffin1 (AUTHOR), Phan, Hong Kim T.1 (AUTHOR), Singampalli, Kavya L.1,2 (AUTHOR), Birla, Ravi K.3,4 (AUTHOR), Connell, Jennifer P.1 (AUTHOR), Keswani, Sundeep G.3,4 (AUTHOR), Grande-Allen, K. Jane1 (AUTHOR) grande@rice.edu
Source: Annals of Biomedical Engineering. Nov2024, Vol. 52 Issue 11, p2932-2947. 16p.
Subjects: Shearing force, Human phenotype, Vascular grafts, Protein expression, Resorption (Physiology)
Abstract: Macrophages are innate immune cells that are known for their extreme plasticity, enabling diverse phenotypes that lie on a continuum. In a simplified model, they switch between pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes depending on surrounding microenvironmental cues, which have been implicated in disease outcomes. Although considerable research has been focused on macrophage response to biochemical cues and mechanical signals, there is a scarcity of knowledge surrounding their behavior in response to shear stress. In this study, we applied varying magnitudes of shear stress on human monocyte-derived macrophages (MDMs) using a cone-and-plate viscometer and evaluated changes in morphology, gene expression, protein expression, and cytokine secretion over time. MDMs exposed to shear stress exhibited a rounder morphology compared to statically-cultured controls. RT-qPCR results showed significant upregulation of TNF-α, and analysis of cytokine release revealed increased secretion of IL-8, IL-18, fractalkine, and other chemokines. The upregulation of pro-inflammatory factors was evident with both increasing magnitudes of shear and time. Taken together, these results indicate that prolonged shear exposure induced a pro-inflammatory phenotype in human MDMs. These findings have implications for medical technology development, such as in situ vascular graft design wherein macrophages are exposed to shear and have been shown to affect graft resorption, and in delineating disease pathophysiology, for example to further illuminate the role of macrophages in atherosclerosis where shear is directly related to disease outcome. [ABSTRACT FROM AUTHOR]
Copyright of Annals of Biomedical Engineering is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Shear Stress Induces a Time-Dependent Inflammatory Response in Human Monocyte-Derived Macrophages.
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  Data: <searchLink fieldCode="JN" term="%22Annals+of+Biomedical+Engineering%22">Annals of Biomedical Engineering</searchLink>. Nov2024, Vol. 52 Issue 11, p2932-2947. 16p.
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  Data: <searchLink fieldCode="DE" term="%22Shearing+force%22">Shearing force</searchLink><br /><searchLink fieldCode="DE" term="%22Human+phenotype%22">Human phenotype</searchLink><br /><searchLink fieldCode="DE" term="%22Vascular+grafts%22">Vascular grafts</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+expression%22">Protein expression</searchLink><br /><searchLink fieldCode="DE" term="%22Resorption+%28Physiology%29%22">Resorption (Physiology)</searchLink>
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  Label: Abstract
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  Data: Macrophages are innate immune cells that are known for their extreme plasticity, enabling diverse phenotypes that lie on a continuum. In a simplified model, they switch between pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes depending on surrounding microenvironmental cues, which have been implicated in disease outcomes. Although considerable research has been focused on macrophage response to biochemical cues and mechanical signals, there is a scarcity of knowledge surrounding their behavior in response to shear stress. In this study, we applied varying magnitudes of shear stress on human monocyte-derived macrophages (MDMs) using a cone-and-plate viscometer and evaluated changes in morphology, gene expression, protein expression, and cytokine secretion over time. MDMs exposed to shear stress exhibited a rounder morphology compared to statically-cultured controls. RT-qPCR results showed significant upregulation of TNF-α, and analysis of cytokine release revealed increased secretion of IL-8, IL-18, fractalkine, and other chemokines. The upregulation of pro-inflammatory factors was evident with both increasing magnitudes of shear and time. Taken together, these results indicate that prolonged shear exposure induced a pro-inflammatory phenotype in human MDMs. These findings have implications for medical technology development, such as in situ vascular graft design wherein macrophages are exposed to shear and have been shown to affect graft resorption, and in delineating disease pathophysiology, for example to further illuminate the role of macrophages in atherosclerosis where shear is directly related to disease outcome. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
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  Data: <i>Copyright of Annals of Biomedical Engineering is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1007/s10439-024-03546-5
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        Text: English
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        StartPage: 2932
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      – SubjectFull: Shearing force
        Type: general
      – SubjectFull: Human phenotype
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      – SubjectFull: Vascular grafts
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      – SubjectFull: Protein expression
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      – SubjectFull: Resorption (Physiology)
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      – TitleFull: Shear Stress Induces a Time-Dependent Inflammatory Response in Human Monocyte-Derived Macrophages.
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              M: 11
              Text: Nov2024
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              Y: 2024
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