title: Aggregation of mononuclear and red blood cells through an {alpha}4{beta}1-Lu/basal cell adhesion molecule interaction in sickle cell disease.
abstract: 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.
  
  
  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.
authors.affiliation: INSERM, UMRS 665, INTS, 6 rue Alexandre Cabanel, 75015 Paris, France. wassim.el-nemer@inserm.fr.
authors.forename: Vicky
authors.initials: V
authors.lastname: Chaar
authors.forename: Julien
authors.initials: J
authors.lastname: Picot
authors.forename: Olivier
authors.initials: O
authors.lastname: Renaud
authors.forename: Pablo
authors.initials: P
authors.lastname: Bartolucci
authors.forename: Ruben
authors.initials: R
authors.lastname: Nzouakou
authors.forename: Dora
authors.initials: D
authors.lastname: Bachir
authors.forename: Frédéric
authors.initials: F
authors.lastname: Galactéros
authors.forename: Yves
authors.initials: Y
authors.lastname: Colin
authors.forename: Caroline
authors.initials: C
authors.lastname: Le Van Kim
authors.forename: Wassim
authors.initials: W
authors.lastname: El Nemer
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000986:Antisickling Agents / Q000008:administration & dosage; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002449:Cell Aggregation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004912:Erythrocytes / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D039041:Integrin alpha4beta1 / Q000378:metabolism*; D008188:Lutheran Blood-Group System / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology
chemical_list: D000986:Antisickling Agents; C090228:BCAM protein, human; D015815:Cell Adhesion Molecules; D039041:Integrin alpha4beta1; D008188:Lutheran Blood-Group System; D006918:Hydroxyurea