A systemic mechanism of increased transendothelial migration of leukocytes through the blood-brain barrier in hepatic encephalopathy |
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| Institution: | 1. Sorbonne Université, INSERM, Centre de recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), F-75012 Paris, France;2. AP-HP.Sorbonne Université, Hôpital Pitié-Salpêtrière, Service d''Hépato-Gastroentérologie, Unité de Soins Intensifs d''Hépatologie, Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, F-75013 Paris, France;3. AP-HP.Sorbonne Université, Hôpital Saint-Antoine, Service d''Anatomo-Pathologie, Service d''Hépatologie, Centre de Référence Maladie Rare (CRMR) Maladies Inflammatoires des Voies Biliaires-Hépatites Auto-immunes (MIVB-H), Service de Biochimie, F-75012 Paris, France;4. INSERM U 1016, Institut Cochin, Paris, France;5. AP-HP.Sorbonne Université, Hôpital Pitié-Salpêtrière, Département de Neurologie, Unité de Médecine Intensive Réanimation à Orientation Neurologique, Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, Groupe de Recherche Clinique en REanimation et Soins intensifs du Patient en Insuffisance Respiratoire aiguE (GRC-RESPIRE), F-75013 Paris, France;1. MRI Department, the First Affiliated Hospital of Henan University of Chinese Medicine, No 19 Renmin Road, Zhengzhou, Henan, China;2. Department of Radiology, Gold Coast University Hospital, Queensland, Australia;1. Registre des tumeurs, Parc Euromedecine, 208 rue des Apothicaires 34298 Montpellier, France;2. Research Unit INSERM University of Montpellier, IDESP Institute Desbrest of Epidemiology and Public Health, Montpellier, France;3. Department of Digestive surgery, CHU Carémeau, Place du Pr Debré, 30 090 Nîmes, France;1. Paris University; Siric CARPEM, Assistance Publique - Hôpitaux de Paris, Department of Gastroenterology and Digestive Oncology, Hôpital Européen Georges Pompidou, Paris, France;2. Paris University; Assistance Publique - Hôpitaux de Paris, Pathology Department, Hôpital Européen GeorgesPompidou, Paris, France;3. Paris University; Assistance Publique - Hôpitaux de Paris, Dermatology Department, Hôpital Beaujon, Clichy, France;1. Department of Digestive and Surgical Oncology, University Hospital, Dijon, France;2. Digestive Cancer Registry of Burgundy, Dijon, France;3. Department of Medical Oncology, Georges-Francois Leclerc Centre, Dijon, France;4. Department of Geriatrics and Internal Medicine, University Hospital, Dijon, France;5. Department of Digestive and Surgical Oncology, University Hospital, Dijon, France;1. Department of Hepatology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China;2. Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China |
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| Abstract: | BackgroundHepatic encephalopathy (HE) is a frequent neurological complication of cirrhosis. Evidence suggests a synergic pathophysiological implication of hyperammonemia and systemic inflammation. In addition, the blood-brain barrier (BBB) permeability can be impaired in cirrhotic patients, notably in those displaying HE. We hypothesized that systemic inflammation could trigger leukocytes transendothelial migration (TEM) through the BBB in cirrhotic patients and especially those with HE.MethodsWe studied the effects of patients’ plasma on the TEM of the leukocyte U937 cell line in vitro, using a validated BBB model (hCMEC/D3 cell line). We compared TEM of U937 leukocytes across hCMEC/D3 monolayer incubated with the plasma of i) patients with cirrhosis without HE, ii) patients with cirrhosis and HE, iii) healthy controls.ResultsWe show that the plasma of cirrhotic patients with HE enhances TEM of U937 leukocytes across hCMEC/D3 BBB model. We found a correlation between U937 TEM on the one hand, the West-Haven score and ammonemia on the other one. A trend towards a correlation between U937 TEM and PS-100Beta in plasma, a marker of BBB solute's permeability increase, was also found.ConclusionThese findings suggest that circulating factors could increase leukocytes TEM in cirrhotic patients and contribute to the increased BBB permeability that has been described in cirrhotic patients with HE. |
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