Emergence of anti-red blood cell antibodies triggers red cell phagocytosis by activated macrophages in a rabbit model of Epstein-Barr virus-associated hemophagocytic syndrome.
Hemophagocytic syndrome (HPS) is a fatal complication frequently associated with viral infections. In childhood HPS, Epstein-Barr virus (EBV) is the major causative agent, and red blood cells (RBCs) are predominantly phagocytosed by macrophages. To investigate the mechanism of RBC phagocytosis triggered by EBV infection, we adopted a rabbit model of EBV-associated HPS previously established by using Herpesvirus papio (HVP). The kinetics of virus-host interaction was studied. Using flow cytometry, we detected the emergence of antibody-coated RBCs, as well as anti-platelet antibodies, at peak virus load period at weeks 3 to 4 after HVP injection, and the titers increased thereafter. The presence of anti-RBCs preceded RBC phagocytosis in tissues and predicted the full-blown development of HPS. The anti-RBC antibodies showed cross-reactivity with Paul-Bunnell heterophile antibodies. Preabsorption of the HVP-infected serum with control RBCs removed the majority of anti-RBC activities and remarkably reduced RBC phagocytosis. The RBC phagocytosis was specifically mediated via an Fc fragment of antibodies in the presence of macrophage activation. Therefore, the emergence of anti-RBC antibodies and the presence of macrophage activation are both essential in the development of HPS. Our observations in this animal model provide a potential mechanism for hemophagocytosis in EBV infection.
Hsieh
Wen-Chuan
WC
Division of Clinical Research, National Health Research Institutes, 367, Shen-Li Rd., Tainan, Taiwan.
Chang
Yao
Y
Hsu
Mei-Chi
MC
Lan
Bau-Shin
BS
Hsiao
Guan-Chung
GC
Chuang
Huai-Chia
HC
Su
Ih-Jen
IJ
D000818:Animals; D000910:Antibodies, Heterophile; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D003429:Cross Reactions; D004195:Disease Models, Animal; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000821:virology; D004912:Erythrocytes / Q000276:immunology* / Q000473:pathology; D005434:Flow Cytometry; D006566:Herpesviridae Infections / Q000276:immunology; D006790:Host-Parasite Interactions / Q000276:immunology*; D007150:Immunohistochemistry; D051359:Lymphohistiocytosis, Hemophagocytic / Q000276:immunology* / Q000821:virology; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology*; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018139:Simplexvirus / Q000276:immunology
D000910:Antibodies, Heterophile; D001323:Autoantibodies