Soothing touch of CD31 protects endothelium during cellular immune responses

Thaunat, Olivier

doi:10.1073/pnas.1517580112

Cited by 7 publications

(4 citation statements)

References 13 publications

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“…CD31, also known as PECAM1 (platelet endothelial cell adhesion molecule 1), is a glycoprotein that is expressed on endothelial cells, platelets, and leukocytes and is involved many physiologic and pathologic pathways, including leukocyte migration, angiogenesis, maintenance of vascular integrity, and immunoregulatory roles in endothelial and hematopoietic cells. 11,32,39 CD31 is positively expressed in vascular neoplasms of many species, including dogs, cats, NHP, and humans, 7,20,32,41 and the tumor in our case exhibited strong positive cytoplasmic staining. Vimentin is a filamentous protein that is expressed on normal mesenchymal cells and plays a role in maintenance of cellular integrity.…”

Section: Discussionsupporting

confidence: 49%

Hepatic Hemangiosarcoma in a Cynomolgus Macaque (Macaca fascicularis)

et al. 2019

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An experimentally naïve, 9-y-old intact male cynomolgus macaque (Macaca fascicularis) was reported by the animal care staff for bleeding from an unknown origin. Cage-side assessment revealed that the patient had lost 5 to 10 mL of blood, which was pooled on the floor of the primary enclosure. He exhibited no visible outward signs of injury and was singly housed at the time. The macaque was sedated with ketamine (4 mg/kg IM) and dexmedetomidine (0.05 mg/kg IM) for examination and further diagnostics.

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Section: Discussionsupporting

confidence: 49%

Hepatic Hemangiosarcoma in a Cynomolgus Macaque (Macaca fascicularis)

et al. 2019

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“…It was known that CD31 is highly expressed on endothelial cells ( 31 ). To increase the targeting of ORI-NPs to the epithelia of lung tissues, we conjugated such NPs to an anti-CD31 antibody (anti-CD31-ORI-NPs) via covalent coupling to terminal COOH end groups on PEG.…”

Section: Resultsmentioning

confidence: 99%

Oridonin inhibits inflammation of epithelial cells via dual-targeting of CD31 Keap1 to ameliorate acute lung injury

et al. 2023

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IntrodcutionAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of COVID-19 mortality. However, drug delivery to lung tissues is impeded by endothelial cell barriers, limiting the efficacy of existing treatments. A prompt and aggressive treatment strategy is therefore necessary.MethodsWe assessed the ability of anti-CD31-ORI-NPs to penetrate endothelial cell barriers and specifically accumulate in lung tissues using an animal model. We also compared the efficacy of anti-CD31-ORI-NPs to that of free oridonin in ameliorating acute lung injury and evaluated the cytotoxicity of both treatments on endothelial cells.ResultsCompared to free ORI, the amount of anti-CD31-ORI-NPs accumulated in lung tissues increase at least three times. Accordingly, anti-CD31-ORI-NPs improve the efficacy three times on suppressing IL-6 and TNF-a secretion, ROS production, eventually ameliorating acute lung injury in animal model. Importantly, anti-CD31-ORI-NPs significantly decrease the cytotoxicity at least two times than free oridonin on endothelial cells.DiscussionOur results from this study will not only offer a novel therapeutic strategy with high efficacy and low toxicity, but also provide the rational design of nanomaterials of a potential drug for acute lung injury therapy.

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“…Another special feature of the endothelium is its resistance to cell death, as it needs to withstand high concentrations of inflammatory mediators during inflammation while maintaining its integrity. This becomes evident in patients with allograft rejection, where host effector T cells damage the donor organ while the donor capillary endothelium remains relatively unharmed [82]. Remarkably, PECAM‐1 is sufficient to confer resistance against TNF and cytotoxic T lymphocytes to vascular endothelium, which requires both of its ITIMs and correlates with SHP‐2 recruitment and Erk/Akt pathway activation [83].…”

Section: Inhibitory Receptors On Endothelial Cellsmentioning

confidence: 99%

Sensing context: Inhibitory receptors on non‐hematopoietic cells

Richthofen

Meyaard

2023

Eur J Immunol

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Similar to immune cells, non‐hematopoietic cells recognize microbial and endogenous threats. Their response to these stimuli is dependent on the environmental context. For example, intact intestinal epithelium expresses pattern recognition receptors (PRRs) but should tolerate commensal bacteria, while damaged epithelium should respond promptly to initiate an immune response. This indicates that non‐hematopoietic cells possess mechanisms to sense environmental context and regulate their responses. Inhibitory receptors provide context sensing to immune cells. For instance, they raise the threshold for activation to prevent overzealous immune activation to harmless stimuli. Inhibitory receptors are typically studied on hematopoietic cells, but several of these receptors are expressed on non‐hematopoietic cells. Here, we review evidence for the regulation of non‐hematopoietic cells by inhibitory receptors, focusing on epithelial and endothelial cells. We explain that inhibitory receptors on these cells can sense a wide range of signals, including cell‐cell adhesion, cell‐matrix adhesion, and apoptotic cells. More importantly, they regulate various functions on these cells, including immune activation, proliferation, and migration. In conclusion, we propose that inhibitory receptors provide context to non‐hematopoietic cells by fine tuning their response to endogenous or microbial stimuli. These findings prompt to investigate the functions of inhibitory receptors on non‐hematopoietic cells more systematically.

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Soothing touch of CD31 protects endothelium during cellular immune responses

Cited by 7 publications

References 13 publications

Hepatic Hemangiosarcoma in a Cynomolgus Macaque (Macaca fascicularis)

Hepatic Hemangiosarcoma in a Cynomolgus Macaque (Macaca fascicularis)

Oridonin inhibits inflammation of epithelial cells via dual-targeting of CD31 Keap1 to ameliorate acute lung injury

Sensing context: Inhibitory receptors on non‐hematopoietic cells

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