Platelet-bound lipopolysaccharide enhances Fc receptor-mediated phagocytosis of IgG-opsonized platelets.
Platelets express Toll-like receptor 4 (TLR4), and this has been shown to be responsible for the thrombocytopenia induced by lipopolysaccharide (LPS) administration in vivo. We studied the role of LPS in mediating platelet phagocytosis by THP-1 cells in vitro by flow cytometry. Opsonization of platelets with an IgG monoclonal (W6/32) antibody or with IgG autoantibody-positive sera from patients with autoimmune thrombocytopenia (AITP) significantly enhanced platelet phagocytosis (P < .001). In contrast, platelet phagocytosis did not occur if platelets were bound with only LPS. If, however, the LPS-bound platelets were also opsonized with either W6/32 or autoantibody-positive sera with titers greater than 4, there was a significant and synergistic increase in Fc-dependent platelet phagocytosis (P < .001, P = .003, P = .048, and P = .047). These results suggest that, in the presence of antiplatelet antibodies, bacterial products can significantly alter platelet phagocytosis, and this may have relevance to how Gram-negative infections enhance platelet destruction in some patients with AITP.
Semple
John W
JW
Department of Laboratory Medicine, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, Canada. semplej@smh.toronto.on.ca
Aslam
Rukhsana
R
Kim
Michael
M
Speck
Edwin R
ER
Freedman
John
J
D000911:Antibodies, Monoclonal / Q000737:chemistry; D016824:Antigens, Human Platelet / Q000737:chemistry; D001323:Autoantibodies / Q000737:chemistry; D001792:Blood Platelets / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000378:metabolism*; D009895:Opsonin Proteins / Q000737:chemistry*; D010587:Phagocytosis; D010974:Platelet Aggregation; D011961:Receptors, Fc / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D000911:Antibodies, Monoclonal; D016824:Antigens, Human Platelet; D001323:Autoantibodies; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D009895:Opsonin Proteins; D011961:Receptors, Fc; D051197:Toll-Like Receptor 4