Hepatosplenic phagocytic cells indirectly contribute to anti-PEG IgM production in the accelerated blood clearance (ABC) phenomenon against PEGylated liposomes: Appearance of an unexplained mechanism in the ABC phenomenon.

Abstract

The accelerated blood clearance (ABC) phenomenon, caused in large degree via in vivo anti-PEG IgM production, is one of obstacles for development of PEGylated liposome and protein formulations, due to decreased efficiency and/or side effects such as anaphylaxis upon repeat administrations. We have shown in murine ABC models that splenectomy suppressed the level of anti-PEG IgM production induced by PEGylated liposomes, indicating that murine splenic B cells play an important role in its production. However, splenectomy did not completely inhibit production of anti-PEG IgM, suggesting that other cells may contribute to its production in the ABC phenomenon. In this study, we examined the contribution of hepatosplenic phagocytic cells to anti-PEG IgM production and clearance of PEGylated liposomes during the ABC phenomenon. Depletion of hepatosplenic phagocytic cells by pretreatment of mice with clodronate-containing non-PEGylated liposomes suppressed anti-PEG IgM production to a considerable degree, without a change in the number of splenic B cells, and attenuated the enhanced clearance of second dose of PEGylated liposomes. These results suggest that hepatosplenic phagocytic cells, in addition to splenic B cells, contribute to the production of anti-PEG IgM and the ABC phenomenon against PEGylated liposomes. The mechanism whereby splenic B cells interact with hepatosplenic phagocytic cells to produce anti-PEG IgM, upon administration of an initial dose of PEGylated liposomes remains to be elucidated.

• Authors: Marwa Mohamed El Sayed, Haruka Takata, Taro Shimizu, Yoshino Kawaguchi, Amr S Abu Lila, Nehal E Elsadek, Eman Alaaeldin, Yu Ishima, Hidenori Ando, Amal Kamal, Hatem A Sarhan, Tatsuhiro Ishida
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 323 Pg. 102-109 (07 10 2020) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 32278827 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Immunoglobulin M
• Liposomes
• Polyethylene Glycols

Topics

• Animals
• Immunoglobulin M
• Liposomes
• Mice
• Phagocytes
• Polyethylene Glycols
• Spleen