β1-integrin mediates pressure-stimulated phagocytosis

Bhalla, S. R.; Shiratsuchi, Hiroe; Craig, David; Basson, Marc D.

doi:10.1016/j.amjsurg.2009.07.006

Cited by 9 publications

(11 citation statements)

References 39 publications

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“…Although the stimulation of microglial phagocytosis by pressure has not previously been described, we and others have previously described the ability of increases in extracellular pressure to stimulate the uptake of serum-opsonized latex beads, IgG complex, tumor cell fragments, and Klebsiella pneumonia 29, 3027, 28, 40, 42, 43, 60 . The mechanisms of this effect, and whether more specific microglial endocytosis is similarly affected by increased extracellular pressure awaits study.…”

Section: Discussionmentioning

confidence: 85%

“…30 Activation of alveolar macrophages by pressure has also been demonstrated in vitro and in vivo 4041 , including a trend toward increased macrophage phagocytosis of Klebsiella pneumonia in response to pressure and significant cytokine activation 40 Fibroblasts and dendritic cells also display increased phagocytosis in response to increased pressure, although propofol was not investigated in those studies. 42, 43 . Increased extracellular pressure increases phagocytosis in monocytes and macrophages by inhibiting FAK and ERK.…”

Section: Discussionmentioning

confidence: 99%

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Propofol’s effects on phagocytosis, proliferation, nitrate production, and cytokine secretion in pressure-stimulated microglial cells

Dymond

Yuan

et al. 2011

Surgery

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Introduction Intracranial hypertension frequently complicates severe traumatic brain injury (TBI) and may be associated with poor outcomes. TBI induces a neuroinflammatory response by microglial activation and upregulation of proinflammatory cytokines such as interleukin (IL)-1β, tumor necrosis factor alpha (TNF-α,) and interleukin-6 (IL-6). To elucidate the effect of elevated intracranial pressure on microglial function, we studied the effects of increased extracellular pressure on primary human microglial cell phagocytosis, proliferation, cytokine secretion and total nitrate production. In addition, since many patients receive propofol during anesthesia or intensive care unit sedation, we evaluated whether propofol alters the effects of pressure. Methods Human microglial cells (HMG030) were pretreated with (2.5–20μg/ml) propofol or intralipid as a vehicle control were incubated at ambient atmospheric pressure or at 15 or 30 mmHg increased pressure for 2 hours for phagocytosis assays or 24 hours for proliferation, cytokine secretion and total nitrate production studies. Phagocytosis was determined by incorporation of intracellular fluorescent latex beads. TNF-α, IL1-β and IL-6 were assayed by sandwich ELISA, and total nitrate by Greiss reagent. Results Increased extracellular pressure stimulated phagocytosis vs. untreated microglial cells or cells treated with an intralipid vehicle control. In fact, propofol also stimulated microglial phagocytosis at ambient pressure. However, increased pressure reduced phagocytosis in the presence of propofol. Pressure also increased microglial TNF-α and IL-1β secretion and propofol pretreatment blocked the pressure-stimulated effect. However, IL-6 production was not altered either by pressure or propofol. Pressure also induced total nitrate secretion and propofol pretreatment decreased basal as well as pressure-induced microglial nitrate production. Conclusion Extracellular pressures consistent with increased intracranial pressure after head injury activate inflammatory signals in human primary microglial cells in vitro, stimulating phagocytosis, proliferation, and TNF-α, IL-1β, and total nitrate secretion but not affecting IL-6. Such inflammatory events may contribute to the worsened prognosis of traumatic brain injury after increased intracranial pressure. Since propofol alleviated these potentially pro-inflammatory effects, these results raise the possibility that the inflammatory cascade activated by intracranial pressure may be targeted by propofol in patients with increased intracranial pressure after TBI.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Propofol’s effects on phagocytosis, proliferation, nitrate production, and cytokine secretion in pressure-stimulated microglial cells

Dymond

Yuan

et al. 2011

Surgery

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“…Ingber (10) postulated that physical forces like pressure change the conformation of the cytoskeleton and the signal molecules associated with it. We have previously identified numerous intracellular kinases modulated by pressure in epithelial cells (8)(22), macrophages (21) monocytes (21) and fibroblasts (4). Thus it would not be unreasonable to hypothesize that alcohol-pressure interactions might be mediated by structural conformational changes in one or more intracellular signal molecules.…”

Section: Discussionmentioning

confidence: 99%

“…We studied 30 mm Hg, resembling in vivo ICP after TBI. We previously described effects of similar pressures on cell proliferation and signaling in microglial cells (24), epithelial cells (8, 22), macrophages (21), monocytes (21) and fibroblasts (4). Pressures of 15 mmHg and 30 mmHg above ambient have similar effects on microglial cells (24).…”

Section: Introductionmentioning

confidence: 99%

Effects of extracellular pressure and alcohol on the microglial response to inflammatory stimulation

Chaturvedi

Zhang

Basson

2012

The American Journal of Surgery

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TBI induces a neuroinflammatory response frequently associated with increased intracranial pressure (ICP). We investigated the effects of alcohol and increased extracellular pressure on murine BV-2 microglial proliferation and cytokine responses to lipopolysaccharide (LPS) stimulation. BV-2 cells were cultured under 0 or 30mmHg increased extracellular pressure without or with ethanol (100mM) or LPS (10ng/ml) for 24 hours. We assessed cell proliferation via MTS assay and secretion of the pro-inflammatory cytokines TNF-α, IL-6, and MCP-1 by ELISA. Increased pressure and LPS stimulation each promoted proliferation. Ethanol pretreatment blocked these effects. Basal TNF-α and IL-6 secretion were at the limits of delectability. Basal MCP-1 production was stimulated by pressure, which was blocked by ethanol. Even this low LPS dose stimulated microglial secretion of TNF-α, IL-6 and MCP-1. Pressure inhibited LPS-stimulated production of these proinflammatory cytokines, while ethanol pretreatment blocked LPS-stimulated cytokine production. The combination of pressure and ethanol further reduced TNF-α, IL-6 and MCP-1 secretion by LPS-stimulated microglial cells. Alcohol’s anti-inflammatory effects may contribute to the reduced TBI mortality that some have described in acutely intoxicated patients, while pressure downregulation of inflammatory cytokine release could create a negative feedback that ameliorates inflammation in TBI.

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“…Markers for M1 and M2 macrophages have been quantified in unfractionated cells harvested from wounds to determine their influence on wound healing [22, 23]. Several physical factors have been reported to regulate macrophage polarization, including cell shape [24], scaffold pore size [25, 26], and mechanical forces applied to scaffolds, which stimulate inflammation through activation of focal adhesions [18, 27] and integrins [28]. However, the effects of substrate modulus on macrophage polarization have not been extensively investigated [29, 30].…”

Section: Introductionmentioning

confidence: 99%

Substrate modulus of 3D-printed scaffolds regulates the regenerative response in subcutaneous implants through the macrophage phenotype and Wnt signaling

Merkel

Sterling

et al. 2015

Biomaterials

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The growing need for therapies to treat large cutaneous defects has driven recent interest in the design of scaffolds that stimulate regenerative wound healing. While many studies have investigated local delivery of biologics as a restorative approach, an increasing body of evidence highlights the contribution of the mechanical properties of implanted scaffolds to wound healing. In the present study, we designed poly(ester urethane) scaffolds using a templated-Fused Deposition Modeling (t-FDM) process to test the hypothesis that scaffolds with substrate modulus comparable to that of collagen fibers enhance a regenerative versus a fibrotic response. We fabricated t-FDM scaffolds with substrate moduli varying from 5 – 266 MPa to investigate the effects of substrate modulus on healing in a rat subcutaneous implant model. Angiogenesis, cellular infiltration, collagen deposition, and directional variance of collagen fibers were maximized for wounds treated with scaffolds having a substrate modulus (Ks = 24 MPa) comparable to that of collagen fibers. The enhanced regenerative response in these scaffolds was correlated with down-regulation of Wnt/β-catenin signaling in fibroblasts, as well as increased polarization of macrophages toward the restorative M2 phenotype. These observations highlight the substrate modulus of the scaffold as a key parameter regulating the regenerative versus scarring phenotype in wound healing. Our findings further point to the potential use of scaffolds with substrate moduli tuned to that of the native matrix as a therapeutic approach to improve cutaneous healing.

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β1-integrin mediates pressure-stimulated phagocytosis

Cited by 9 publications

References 39 publications

Propofol’s effects on phagocytosis, proliferation, nitrate production, and cytokine secretion in pressure-stimulated microglial cells

Propofol’s effects on phagocytosis, proliferation, nitrate production, and cytokine secretion in pressure-stimulated microglial cells

Effects of extracellular pressure and alcohol on the microglial response to inflammatory stimulation

Substrate modulus of 3D-printed scaffolds regulates the regenerative response in subcutaneous implants through the macrophage phenotype and Wnt signaling

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