Amniotic Membrane Transplantation Induces Apoptosis in T Lymphocytes in Murine Corneas with Experimental Herpetic Stromal Keratitis

Bauer, Dirk; Wasmuth, Susanne; Hennig, Maren; Baehler, Hanna; Steuhl, Klaus‐Peter; Heiligenhaus, Arnd

doi:10.1167/iovs.08-3041

Cited by 44 publications

(35 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2). Collectively, these data corroborate the previous studies based on AM (33,34,40) and AME (41) while beginning to explain the mechanism of their anti-inflammatory effects via promotion of apoptosis of activated neutrophils (33,34,37), macrophages (35,37,39), and probably lymphocytes (36).…”

Section: Discussionsupporting

confidence: 88%

“…30 -32). Application of cryopreserved human AM reduces infiltration of neutrophils in the excimer-ablated rabbit corneal stroma while promoting apoptosis of neutrophils (33,34); traps and causes apoptosis of monocytes and macrophages during the treatment of human corneal epithelial defects (35); induces rapid regression of corneal stromal edema and inflammation by reducing infiltration of lymphocytes (36), neutrophils (37), and macrophages (37,38); and promotes M2a phenotype in the corneal stroma of murine HSV-1 necrotizing keratitis (39). These in vivo data are supported by in vitro findings that human AM induces apoptosis of IFN-␥ activated monocyte/macrophage RAW264.7 cells (40).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Immobilized Heavy Chain-Hyaluronic Acid Polarizes Lipopolysaccharide-activated Macrophages toward M2 Phenotype

He¹,

Zhang²,

Tighe³

et al. 2013

Journal of Biological Chemistry

115

118

View full text Add to dashboard Cite

Background: HC-HA is a unique anti-inflammatory matrix different from hyaluronic acid (HA). Results: Soluble HC-HA induces apoptosis of inflammatory neutrophils and macrophages, and immobilized HC-HA promotes M2 polarization upon LPS/TLR ligation while both enhancing macrophage phagocytosis. Conclusion: HC-HA exerts its anti-inflammatory action using multiple mechanisms. Significance: HC-HA is the first known matrix component to polarize M2b.Despite the known anti-inflammatory effect of amniotic membrane, its action mechanism remains largely unknown. HC-HA complex (HC-HA) purified from human amniotic membrane consists of high molecular weight hyaluronic acid (HA) covalently linked to the heavy chain (HC) 1 of inter-␣-trypsin inhibitor. In this study, we show that soluble HC-HA also contained pentraxin 3 and induced the apoptosis of both formyl-Met-Leu-Phe or LPS-activated neutrophils and LPS-activated macrophages while not affecting the resting cells. This enhanced apoptosis was caused by the inhibition of cell adhesion, spreading, and proliferation caused by HC-HA binding of LPS-activated macrophages and preventing adhesion to the plastic surface. Preferentially, soluble HC-HA promoted phagocytosis of apoptotic neutrophils in resting macrophages, whereas immobilized HC-HA promoted phagocytosis in LPSactivated macrophages. Upon concomitant LPS stimulation, immobilized HC-HA but not HA polarized macrophages toward the M2 phenotype by down-regulating IRF5 protein and preventing its nuclear localization and by down-regulating IL-12, TNF-␣, and NO synthase 2. Additionally, IL-10, TGF-␤1, peroxisome proliferator-activated receptor ␥, LIGHT (TNF superfamily 14), and sphingosine kinase-1 were up-regulated, and such M2 polarization was dependent on TLR ligation. Collectively, these data suggest that HC-HA is a unique matrix component different from HA and uses multiple mechanisms to suppress M1 while promoting M2 phenotype. This anti-inflammatory action of HC-HA is highly desirable to promote wound healing in diseases heightened by unsuccessful transition from M1 to M2 phenotypes.Inflammation serves as the first host response to real or perceived threats to tissue homeostasis. It is heralded by the recruitment of neutrophils, which eliminate pathogens and damaged tissues before eventually undergoing apoptosis (1-3). These apoptotic neutrophils are then removed by macrophages via phagocytosis, resulting in the restoration and maintenance of anti-inflammatory and tolerogenic milieu (4). On the contrary, delayed neutrophil apoptosis and/or impaired phagocytic clearance of apoptotic neutrophils by macrophages leads to prolonged inflammation that is the hallmark of a number of diseases (5-8). Hence, facilitation of neutrophil apoptosis and phagocytic clearance of apoptotic neutrophils by macrophages is an important strategy to limit inflammation-mediated tissue damage to restore tissue homeostasis (9 -11).Macrophages undergo phenotypic changes to adapt to the transition from proinflammatory to anti-inflammatory states of wou...

show abstract

Section: Discussionsupporting

confidence: 88%

mentioning

confidence: 99%

Immobilized Heavy Chain-Hyaluronic Acid Polarizes Lipopolysaccharide-activated Macrophages toward M2 Phenotype

He¹,

Zhang²,

Tighe³

et al. 2013

Journal of Biological Chemistry

115

118

View full text Add to dashboard Cite

show abstract

“…Then, 10 μg/ mL hIRBP p161-180 peptide, monoclonal antibody (mAb) anti-CD3e (clone 145-2C11; BD Pharmingen, Hamburg, Germany), 5 μg/mL concanavalin A (ConA; Biochrom, Berlin Germany), or medium (control) was added. The supernatant of each well was harvested after 24 h and stored at -80 ° C until use [24,28] .…”

Section: Cell Culturementioning

confidence: 99%

Behavioral Conditioning of Immune Responses with Cyclosporine A in a Murine Model of Experimental Autoimmune Uveitis

Bauer

Busch²,

Pacheco-López³

et al. 2017

Neuroimmunomodulation

Self Cite

View full text Add to dashboard Cite

Objective: We examined the role of behavioral conditioning of immune responses with cyclosporine A (CsA) on the development of Th1/Th17-driven experimental autoimmune uveoretinitis (EAU). Methods: Mice received a 0.2% w/v saccharin solution as conditioned stimulus combined with CsA (20 mg/kg) in 6 association trials at 72-h intervals. For evocation periods, conditioned mice were reexposed to saccharin, whereas the conditioned but not reexposed group received water only. Animals were immunized with human interphotoreceptor-retinoid-binding protein peptide 161-180 (hIRBP_p161-180) peptide in complete Freund adjuvant (CFA) and a concomitant injection of pertussis toxin. Results: In naïve mice subjected to the behavioral conditioning regimen, mitogen-induced interleukin (IL)-2 production was decreased in conditioned mice compared to conditioned but not reexposed animals. Incidence and severity of EAU were not significantly lower in behaviorally conditioned and immunized mice. ELISA analysis of splenocytes revealed a reduced interferon (IFN)-γ/IL-17 ratio in CsA-treated, conditioned but not reexposed, and conditioned animals. The adoptive transfer of antigen-specific splenocytes from animals behaviorally conditioned with CsA to naïve mice decreased the severity of EAU in recipient mice compared to the control group. In vitro activation of splenocytes isolated from immunized mice with agonists targeting TLR2 and NOD2 together with β₂-adrenergic activation (induced by epinephrine, norepinephrine, or salbutamol) resulted in decreased IFN-γ but increased IL-17 immune responses. The β₂-adrenergic antagonist propranolol could restore IFN-γ production, whereas only the norepinephrine-induced increase in IL-17 production was abrogated. Conclusions: We conclude that CsA conditioning in the EAU model mitigates Th1 but enhances Th17 immune responses, and does not ameliorate disease. The results imply that in EAU the mechanism of immune conditioning interacts with CFA components during active immunization, most likely via the TLR2/NOD2 pathway, and induces differentiation of Th17 cells that drive autoimmune diseases.

show abstract

“…(Ellison et al, 2003) Based on the ability of HSV-1 to circumvent the immune response and maintain latency, along with the complexity of immune players that orchestrate signalling cascades leading to a spectrum of disease seen clinically, it is challenging for clinicians to treat HSK effectively. Attempts towards immunomodulation of HSK have been made, ranging from induction of apoptosis in T cells by amniotic membrane transfer, (Bauer et al, 2009) to suppression of chemotaxis and activation of CD4+T cells by targeting chemokine receptors. (Komatsu et al, 2008;Lee, S. K. et al, 2008).…”

Section: Herpes Simplex Virus Type-1 (Hsv-1)mentioning

confidence: 99%

Trafficking of Immune Cells in the Cornea and Ocular Surface

Qazi¹,

Turhan²,

Hamrah³

2012

Advances in Ophthalmology

View full text Add to dashboard Cite

Amniotic Membrane Transplantation Induces Apoptosis in T Lymphocytes in Murine Corneas with Experimental Herpetic Stromal Keratitis

Cited by 44 publications

References 65 publications

Immobilized Heavy Chain-Hyaluronic Acid Polarizes Lipopolysaccharide-activated Macrophages toward M2 Phenotype

Immobilized Heavy Chain-Hyaluronic Acid Polarizes Lipopolysaccharide-activated Macrophages toward M2 Phenotype

Behavioral Conditioning of Immune Responses with Cyclosporine A in a Murine Model of Experimental Autoimmune Uveitis

Trafficking of Immune Cells in the Cornea and Ocular Surface

Contact Info

Product

Resources

About