title: Role of lactadherin in the clearance of phosphatidylserine-expressing red blood cells.
abstract: BACKGROUND
  In red blood cells (RBCs) anionic phospholipids, such as phosphatidylserine, are present in the inner leaflet of the membrane bilayer. Exposure of phosphatidylserine occurs during senescence and during long-term storage of RBCs and is considered as the tag for removal from the circulation by macrophages. Lactadherin is a phosphatidylserine-binding glycoprotein secreted by macrophages that promotes the engulfment of phosphatidylserine-expressing apoptotic lymphocytes. This study investigates the role of lactadherin in the phagocytosis of phosphatidylserine-expressing RBCs.
  
  
  METHODS
  Transbilayer movement of phosphatidylserine was induced in RBCs either by storage beyond 30 days or by treatment with calcium ionophore A23187 and N-ethylmaleimide. Phosphatidylserine-expressing RBCs were incubated with phorbol ester-stimulated THP-1, and phagocytosis was determined by measuring the pseudoperoxidase activity of hemoglobin. The in vivo clearance of phosphatidylserine-enriched RBCs was measured in lactadherin-deficient mice and in their littermate controls.
  
  
  RESULTS
  Lactadherin promoted phagocytosis of phosphatidylserine-expressing RBCs by macrophages in a concentration-dependent manner. Splenic macrophages from lactadherin-deficient mice had diminished capacity to phagocytose phosphatidylserine-expressing RBCs. The life span of RBCs in lactadherin-deficient mice was similar to wild-type littermate controls in vivo. However, when an excess of phosphatidylserine-expressing RBCs were infused, there was only a mild impairment in the clearance in lactadherin-deficient mice compared to wild-type littermate controls.
  
  
  CONCLUSIONS
  These results show that clearance of phosphatidylserine-expressing RBCs is not diminished in a significant way in lactadherin-deficient mice under physiologic conditions and suggest the presence of redundant pathways.
authors.affiliation: Department of Pathology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Dasgupta
authors.forename: Hanan
authors.initials: H
authors.lastname: Abdel-Monem
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Guchhait
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Nagata
authors.forename: Perumal
authors.initials: P
authors.lastname: Thiagarajan
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000032:analysis; D000954:Antigens, Surface / Q000097:blood / Q000502:physiology*; D017209:Apoptosis; D001793:Blood Preservation; D000001:Calcimycin / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D002460:Cell Line; D004492:Edetic Acid / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects*; D005033:Ethylmaleimide / Q000494:pharmacology; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000032:analysis; D006801:Humans; D008262:Macrophage Activation; D051379:Mice; D018345:Mice, Knockout; D008894:Milk Proteins / Q000097:blood; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000097:blood; D013997:Time Factors
chemical_list: D017304:Annexin A5; D000954:Antigens, Surface; C492760:FITC-annexin A5; C098942:MFGE8 protein, human; C490919:Mfge8 protein, mouse; D008894:Milk Proteins; D010718:Phosphatidylserines; D000001:Calcimycin; D004492:Edetic Acid; D016650:Fluorescein-5-isothiocyanate; D002122:Calcium Chloride; D005033:Ethylmaleimide