The long pentraxin PTX3 binds to apoptotic cells and regulates their clearance by antigen-presenting dendritic cells.
Pentraxins are acute-phase proteins produced in vivo during inflammatory reactions. Classical short pentraxins, C-reactive protein, and serum amyloid P component are generated in the liver in response to interleukin (IL)-6. The long pentraxin PTX3 is produced in tissues under the control of primary proinflammatory signals, such as lipopolysaccharide, IL-1 beta, and tumor necrosis factor-alpha, which also promote maturation of dendritic cells (DCs). Cell death commonly occurs during inflammatory reactions. In this study, it is shown that PTX3 specifically binds to dying cells. The binding was dose dependent and saturable. Recognition was restricted to extranuclear membrane domains and to a chronological window after UV irradiation or after CD95 cross-linking-induced or spontaneous cell death in vitro. PTX3 bound to necrotic cells to a lesser extent. Human DCs failed to internalize dying cells in the presence of PTX3, while they took up normally soluble or inert particulate substrates. These results suggest that PTX3 sequesters cell remnants from antigen-presenting cells, possibly contributing to preventing the onset of autoimmune reactions in inflamed tissues. (Blood. 2000;96:4300-4306)
Rovere
P
P
Tumor Immunology Laboratory, Istituto Scientifico H S. Raffaele, Milano, Italy.
Peri
G
G
Fazzini
F
F
Bottazzi
B
B
Doni
A
A
Bondanza
A
A
Zimmermann
V S
VS
Garlanda
C
C
Fascio
U
U
Sabbadini
M G
MG
Rugarli
C
C
Mantovani
A
A
Manfredi
A A
AA
D000210:Acute-Phase Reaction; D034961:Antigens, Nuclear; D017209:Apoptosis / Q000502:physiology*; D002097:C-Reactive Protein / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D019169:Jurkat Cells / Q000378:metabolism / Q000528:radiation effects; D018613:Microscopy, Confocal; D009336:Necrosis; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014466:Ultraviolet Rays; D019014:fas Receptor / Q000502:physiology; D000099153:Pentraxins
D034961:Antigens, Nuclear; D002097:C-Reactive Protein; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D000683:Serum Amyloid P-Component; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D000099153:Pentraxins