Size-Dependent Segregation Controls Macrophage Phagocytosis of Antibody-Opsonized Targets.
Cell
; 174(1): 131-142.e13, 2018 06 28.
Article
em En
| MEDLINE
| ID: mdl-29958103
ABSTRACT
Macrophages protect the body from damage and disease by targeting antibody-opsonized cells for phagocytosis. Though antibodies can be raised against antigens with diverse structures, shapes, and sizes, it is unclear why some are more effective at triggering immune responses than others. Here, we define an antigen height threshold that regulates phagocytosis of both engineered and cancer-specific antigens by macrophages. Using a reconstituted model of antibody-opsonized target cells, we find that phagocytosis is dramatically impaired for antigens that position antibodies >10 nm from the target surface. Decreasing antigen height drives segregation of antibody-bound Fc receptors from the inhibitory phosphatase CD45 in an integrin-independent manner, triggering Fc receptor phosphorylation and promoting phagocytosis. Our work shows that close contact between macrophage and target is a requirement for efficient phagocytosis, suggesting that therapeutic antibodies should target short antigens in order to trigger Fc receptor activation through size-dependent physical segregation.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fagocitose
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Proteínas Opsonizantes
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Macrófagos
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Anticorpos Monoclonais
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Antígenos
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article