Durable and controlled depletion of neutrophils in mice

Nat Commun. 2020 Jun 2;11(1):2762. doi: 10.1038/s41467-020-16596-9.

Abstract

Neutrophils are an essential part of the innate immune system. To study their importance, experimental studies often aim to deplete these cells, generally by injecting anti-Ly6G or anti-Gr1 antibodies. However, these approaches are only partially effective, transient or lack specificity. Here we report that neutrophils remaining after anti-Ly6G treatment are newly derived from the bone marrow, instead of depletion escapees. Mechanistically, newly generated, circulating neutrophils have lower Ly6G membrane expression, and consequently reduced targets for anti-Ly6G-mediated depletion. To overcome this limitation, we develop a double antibody-based depletion strategy that enhances neutrophil elimination by anti-Ly6G treatment. This approach achieves specific, durable and controlled reduction of neutrophils in vivo, and may be suitable for studying neutrophil function in experimental models.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Monoclonal / therapeutic use
  • Antigens, Ly / genetics
  • Antigens, Ly / immunology*
  • Bone Marrow / immunology
  • Cell Death
  • Disease Models, Animal
  • Gene Expression
  • Immunity, Innate
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / immunology*
  • RNA, Messenger / metabolism

Substances

  • Antibodies, Monoclonal
  • Antigens, Ly
  • Ly6G antigen, mouse
  • RNA, Messenger