Identification of a domain (155-183) on CD36 implicated in the phagocytosis of apoptotic neutrophils.
Clearance of apoptotic neutrophils by macrophages is a crucial event following the resolution of acute inflammation. CD36, together with alphavbeta3, has been identified as one of the adhesion molecules on the surface of macrophages implicated in the clearance of polymorphonuclear leukocytes. The domain on CD36 implicated in the phagocytosis of aged neutrophils remains to be elucidated. In this study, COS cells transfected with human CD36 cDNA had a significantly higher capacity to phagocytose human apoptotic neutrophils compared with murine CD36 cDNA. Moreover, monoclonal antibodies 10/5 or OKM5 (epitopes identified on amino acids 155-183) but not monoclonal antibody 13/10 (epitope identified on amino acids 30-76) inhibited phagocytosis of apoptotic neutrophils by COS cells transfected by human CD36. Swapping the human CD36 155-183 domain from human to murine CD36 (human-murine CD36 chimera) imparted to murine CD36-transfected COS cells an increased capacity to phagocytose apoptotic neutrophils. Conversely, when the murine domain 155-183 was inserted in human CD36, a decreased phagocytic capacity was observed. In addition, a synthetic peptide(155-169) but not its scrambled form significantly inhibited phagocytosis. These results identify for the first time a functional domain encompassing amino acids 155-183 on human CD36 implicated in the recognition and phagocytosis of apoptotic neutrophils.
Navazo
M D
MD
INSERM Unit 331, Faculté de Médecine RTH Laènnec, 69372 Lyon, France.
Daviet
L
L
Savill
J
J
Ren
Y
Y
Leung
L L
LL
McGregor
J L
JL
D000818:Animals; D017209:Apoptosis; D018955:CD36 Antigens / Q000737:chemistry*; D002522:Chlorocebus aethiops; D006801:Humans; D009504:Neutrophils / Q000502:physiology*; D010587:Phagocytosis; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013329:Structure-Activity Relationship; D014162:Transfection
D018955:CD36 Antigens; D011993:Recombinant Fusion Proteins