Anti-CD321 antibody immunotherapy protects liver against ischemia and reperfusion-induced injury

Yin, Enzhi; Fukuhara, Takeshi; Takeda, Kazuyoshi; Kojima, Yuko; Fukuhara, Kyoko; Ikejima, Kenichi; Bashuda, Hisashi; Kitaura, Jiro; Yagita, Hideo; Okumura, Ko; Uchida, Koichiro

doi:10.1038/s41598-021-85001-2

Cited by 5 publications

(4 citation statements)

References 47 publications

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“…Results also showed that there was decreased hepatocyte necrosis and apoptosis, and decreased upregulation of TNF-alpha and IL-6 in the mice that received anti-CD321 mAb after liver IRI. Therefore, the blockade of CD321 may serve as a potential therapy in reducing the inflammation and liver injury seen after liver IRI [ 36 ].…”

Section: Neutrophil Trafficking Via Cellular Adhesion Molecules and C...mentioning

confidence: 99%

Role of Immuno-Inflammatory Signals in Liver Ischemia-Reperfusion Injury

Kaltenmeier

Wang

Popp

et al. 2022

Cells

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Ischemia reperfusion injury (IRI) is a major obstacle in liver resection and liver transplantation. The initial step of IRI is mediated through ischemia which promotes the production of reactive oxygen species in Kupffer cells. This furthermore promotes the activation of pro-inflammatory signaling cascades, including tumor necrosis factor-alpha, IL-6, interferon, inducible nitric oxide synthase, TLR9/nuclear-factor kappa B pathway, and the production of damage-associated molecular patterns (DAMPs), such as ATP, histone, high mobility group box 1 (HMGB1), urate, mitochondrial formyl peptides and S100 proteins. With ongoing cell death of hepatocytes during the ischemic phase, DAMPs are built up and released into the circulation upon reperfusion. This promotes a cytokines/chemokine storm that attracts neutrophils and other immune cells to the site of tissue injury. The effect of IRI is further aggravated by the release of cytokines and chemokines, such as epithelial neutrophil activating protein (CXCL5), KC (CXCL1) and MIP-2 (CXCL2), the complement proteins C3a and C5a, mitochondrial-derived formyl peptides, leukotriene B4 and neutrophil extracellular traps (NETs) from migrating neutrophils. These NETs can also activate platelets and form Neutrophil-platelet microthrombi to further worsen ischemia in the liver. In this review we aim to summarize the current knowledge of mediators that promote liver IRI, and we will discuss the role of neutrophils and neutrophil extracellular traps in mediating IRI.

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Section: Neutrophil Trafficking Via Cellular Adhesion Molecules and C...mentioning

confidence: 99%

Role of Immuno-Inflammatory Signals in Liver Ischemia-Reperfusion Injury

Kaltenmeier

Wang

Popp

et al. 2022

Cells

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“…JAM-A (CD321) is involved in cell adhesion and tight junction formation. It can influence inflammatory responses by regulating leukocyte migration and barrier function [ 60 ]. Similarly to E-Cadherin, we found that placental JAMA-A was decreased at all study periods when animals were treated with SHS (1.1-fold, p < 0.002; 1.8-fold, p < 0.0002) or eCigs (both at 1.1-fold, p < 0.02, Figure 7 C).…”

Section: Resultsmentioning

confidence: 99%

Different Lengths of Gestational Exposure to Secondhand Smoke or e-Cigarette Vapor Induce the Development of Placental Disease Symptoms

Kirkham,

Cooper,

Broberg

et al. 2024

Cells

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Exposure to cigarette smoke is known to induce disease during pregnancy. Recent evidence showed that exposure to secondhand smoke (SHS) negatively impacts fetal and placental weights, leading to the development of intrauterine growth restriction (IUGR). Electronic cigarettes (eCigs) represent a phenomenon that has recently emerged, and their use is also steadily rising. Even so, the effects of SHS or eCigs during gestation remain limited. In the present study, we wanted to characterize the effects of SHS or eCig exposure at two different important gestational points during mouse pregnancy. C57/Bl6 mice were exposed to SHS or eCigs via a nose-only delivery system for 4 days (from 14.5 to 17.5 gestational days (dGA) or for 6 days (from 12.5 dGA to 17.5 dGA)). At the time of necropsy (18.5 dGA), placental and fetal weights were recorded, maternal blood pressure was determined, and a dipstick test to measure proteinuria was performed. Placental tissues were collected, and inflammatory molecules in the placenta were identified. Treatment with SHS showed the following: (1) a significant decrease in placental and fetal weights following four days of exposure, (2) higher systolic and diastolic blood pressure following six days of exposure, and (3) increased proteinuria after six days of exposure. Treatment with eCigs showed the following: (1) a significant decrease in placental weight and fetal weight following four or six days of exposure, (2) higher systolic and diastolic blood pressure following six days of exposure, and (3) increased proteinuria after six days of exposure. We also observed different inflammatory markers associated with the development of IUGR or PE. We conclude that the detrimental effects of SHS or eCig treatment coincide with the length of maternal exposure. These results could be beneficial in understanding the long-term effects of SHS or eCig exposure in the development of placental diseases.

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“…Since depleting neutrophils completely may not be clinically feasible, given their role in pathogen clearance and immune surveillance, a better approach may be to block circulating leukocytes from entering the inflammatory site selectively. Indeed, a recent study took this approach when mAb treatment blocked vascular surface marker CD321 (also known as junctional adhesion molecule A or F11R), a marker for transmigration of circulating leukocytes into the inflamed tissue [19 ▪▪ ]. Damage responses by hepatic IRI, evaluated by serum liver enzymes, inflammatory cytokines, and hepatocyte cell death, were all attenuated by the CD321 blockade.…”

Section: Graft-infiltrating Polymorphonuclear Neutrophils and Macroph...mentioning

confidence: 99%

New insights into ischemia-reperfusion injury signaling pathways in organ transplantation

Dery

Kupiec‐Weglinski

2022

Current Opinion in Organ Transplantation

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Purpose of reviewIschemia-reperfusion injury (IRI) leading to allograft rejection in solid organ transplant recipients is a devastating event that compromises graft and patient survival. As our clinical knowledge regarding its definition and presentation has significantly improved over the last years, adequate biomarkers translating to important therapeutic intervention remains a challenge. This review will summarize recent findings in this area.Recent findingsIn the past 18 months, our understanding of organ transplantation IRI has improved. IRI involves a positive amplification feedback loop encompassing damaged cells at the graft site, the activity of redox-sensitive damage-associated molecular patterns, and local sequestration of recipient-derived monocytes, lymphocytes and polymorphonuclear leukocytes, like neutrophils, to sustain the immunological cascade and to enhance the destruction of the foreign tissue. Recent studies have identified critical components leading to IRI, including the oxidation state of high mobility group box 1, a classic danger signal, its role in the Toll-like receptor 4–interleukin (IL)-23–IL-17A signaling axis, and the role of neutrophils and CD321, a marker for transmigration of circulating leukocytes into the inflamed tissue. In addition, recent findings imply that the protective functions mediated by autophagy activation counterbalance the detrimental nucleotide-binding domain-like receptor family, pyrin domain containing 3 inflammasome pathway. Finally, clinical studies reveal the posttransplant variables associated with early allograft dysfunction and IRI.SummaryThe future challenge will be understanding how crosstalk at the molecular and cellular levels integrate prospectively to predict which peri-transplant signals are essential for long-term clinical outcomes.

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Anti-CD321 antibody immunotherapy protects liver against ischemia and reperfusion-induced injury

Cited by 5 publications

References 47 publications

Role of Immuno-Inflammatory Signals in Liver Ischemia-Reperfusion Injury

Role of Immuno-Inflammatory Signals in Liver Ischemia-Reperfusion Injury

Different Lengths of Gestational Exposure to Secondhand Smoke or e-Cigarette Vapor Induce the Development of Placental Disease Symptoms

New insights into ischemia-reperfusion injury signaling pathways in organ transplantation

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