1. Aggregation of mononuclear and red blood cells through an 4 1-Lu/basal cell adhesion molecule interaction in sickle cell disease
- Author
-
Olivier Renaud, Vicky Chaar, Wassim El Nemer, Caroline Le Van Kim, Pablo Bartolucci, Frédéric Galactéros, Dora Bachir, Ruben Nzouakou, Julien Picot, Yves Colin, Protéines de la membrane érythrocytaire et homologues non-érythroides, Université des Antilles et de la Guyane (UAG)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagopole (CITECH), Institut Pasteur [Paris], Unité des maladies génétiques du globule rouge, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Centre de référence des syndromes drépanocytaires majeurs-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and The investigation was supported by the Institut National de la Transfusion Sanguine (INTS), the Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot Paris 7, a grant from the Agence Nationale de la Recherche (ANR, SCADHESION 2007), two grants from Région Ile-de-France (SESAME 2007 no. F-08-1104/R and IMAGOPOLE Project 2007) and a fellowship 'maladies rares' from the Société Française de Médecine Interne (SNFMI) and Actélion.
- Subjects
Male ,Pathology ,Erythrocytes ,Integrin alpha4beta1 ,MESH: Monocytes ,Monocytes ,Blood cell ,MESH: Cell Aggregation ,0302 clinical medicine ,Antisickling Agents ,MESH: Integrin alpha4beta1 ,Hydroxyurea ,MESH: Antisickling Agents ,Cells, Cultured ,Cell Aggregation ,Whole blood ,0303 health sciences ,Hematology ,Cell adhesion molecule ,MESH: Erythrocytes ,Lutheran Blood-Group System ,MESH: Hydroxyurea ,Cell aggregation ,Sickle cell anemia ,3. Good health ,MESH: Lutheran Blood-Group System ,medicine.anatomical_structure ,MESH: Cell Adhesion Molecules ,Original Article ,Female ,MESH: Anemia, Sickle Cell ,MESH: Cells, Cultured ,Adult ,medicine.medical_specialty ,Anemia, Sickle Cell ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Biology ,Peripheral blood mononuclear cell ,MESH: Coculture Techniques ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,030304 developmental biology ,MESH: Humans ,MESH: Adult ,medicine.disease ,Molecular biology ,Coculture Techniques ,MESH: Male ,Red blood cell ,Cell Adhesion Molecules ,MESH: Female ,030215 immunology - Abstract
International audience; BACKGROUND: Abnormal interactions between red blood cells, leukocytes and endothelial cells play a critical role in the occurrence of the painful vaso-occlusive crises associated with sickle cell disease. We investigated the interaction between circulating leukocytes and red blood cells which could lead to aggregate formation, enhancing the incidence of vaso-occlusive crises. DESIGN AND METHODS: Blood samples from patients with sickle cell disease (n=25) and healthy subjects (n=5) were analyzed by imaging and classical flow cytometry after density gradient separation. The identity of the cells in the peripheral blood mononuclear cell layer was determined using antibodies directed specifically against white (anti-CD45) or red (anti-glycophorin A) blood cells. RESULTS: Aggregates between red blood cells and peripheral blood mononuclear cells were visualized in whole blood from patients with sickle cell disease. The aggregation rate was 10-fold higher in these patients than in control subjects. Both mature red blood cells and reticulocytes were involved in these aggregates through their interaction with mononuclear cells, mainly with monocytes. The size of the aggregates was variable, with one mononuclear cell binding to one, two or several red blood cells. Erythroid Lu/basal cell adhesion molecule and α(4)β(1) integrin were involved in aggregate formation. The aggregation rate was lower in patients treated with hydroxycarbamide than in untreated patients. CONCLUSIONS: Our study gives visual evidence of the existence of circulating red blood cell-peripheral blood mononuclear cell aggregates in patients with sickle cell disease and shows that these aggregates are decreased during hydroxycarbamide treatment. Our results strongly suggest that erythroid Lu/basal cell adhesion molecule proteins are implicated in these aggregates through their interaction with α(4)β(1) integrin on peripheral blood mononuclear cells.
- Published
- 2010