Anti-beta2 glycoprotein I antibodies cause inflammation and recruit dendritic cells in platelet clearance.
Scavenger phagocytes are mostly responsible for the in vivo clearance of activated or senescent platelets. In contrast to other particulate substrates, the phagocytosis of platelets does not incite proinflammatory responses in vivo. This study assessed the contribution of macrophages and dendritic cells (DCs) to the clearance of activated platelets. Furthermore, we verified whether antibodies against the beta2 Glycoprotein I (beta2GPI), which bind to activated platelets, influence the phenomenon. DCs did not per se intemalise activated platelets. In contrast, macrophages efficiently phagocytosed platelets. In agreement with the uneventful nature of the clearance of platelets in vivo, phagocytosing macrophages did not release IL-1beta, TNF-alpha, or IL-10, beta2GPI bound to activated platelets and was required for their recognition by anti-beta2GPI antibodies. DCs internalised platelets opsonised by anti-beta2GPI antibodies. The phagocytosis of opsonised platelets determined the release of TNF-alpha and IL-1beta by DCs and macrophages. Phagocytosing macrophages, but not DCs, secreted the antiinflammatory cytokine IL-10. We conclude that anti-beta2GPI antibodies cause inflammation during platelet clearance and shuttle platelet antigens to antigen presenting DCs.
Bondanza
A
A
Immunopathology Unit-Cancer Immunotherapy and Gene Therapy Programme, Istituto Scientifico H S. Raffaele, Milano, Italy.
Manfredi
A A
AA
Zimmermann
V S
VS
Iannacone
M
M
Tincani
A
A
Balestrieri
G
G
Sabbadini
M G
MG
Querini
P R
PR
D000906:Antibodies / Q000302:isolation & purification / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006023:Glycoproteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000302:isolation & purification / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced*; D007375:Interleukin-1 / Q000032:analysis / Q000378:metabolism; D016753:Interleukin-10 / Q000032:analysis / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D010587:Phagocytosis / Q000276:immunology; D015539:Platelet Activation; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism; D053482:beta 2-Glycoprotein I
D000906:Antibodies; D006023:Glycoproteins; D007074:Immunoglobulin G; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D053482:beta 2-Glycoprotein I; D016753:Interleukin-10