PT  - JOURNAL ARTICLE
AU  - Daisuke Takahashi
AU  - Hiroshi Azuma
AU  - Hiromi Sakai
AU  - Keitaro Sou
AU  - Daiko Wakita
AU  - Hideki Abe
AU  - Mitsuhiro Fujihara
AU  - Hirohisa Horinouchi
AU  - Takashi Nishimura
AU  - Koichi Kobayashi
AU  - Hisami Ikeda
TI  - Phagocytosis of Liposome Particles by Rat Splenic Immature Monocytes Makes Them Transiently and Highly Immunosuppressive In Ex Vivo Culture Conditions
AID  - 10.1124/jpet.110.172510
DP  - 2011 Apr 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 42--49
VI  - 337
IP  - 1
4099  - http://jpet.aspetjournals.org/content/337/1/42.short
4100  - http://jpet.aspetjournals.org/content/337/1/42.full
SO  - J Pharmacol Exp Ther2011 Apr 01; 337
AB  - Liposomes reportedly accumulate in monophagocytic systems (MPSs), such as those of the spleen. Accumulation of considerable amounts of liposome in a MPS can affect immunologic response. While developing a liposomal oxygen carrier containing human hemoglobin vesicle (HbV), we identified its suppressive effect on the proliferation of rat splenic T cells. The aim of this study was to elucidate the mechanism underlying that phenomenon and its effect on both local and systemic immune response. For this study, we infused HbV intravenously at a volume of 20% of whole blood or empty liposomes into rats, removed their spleens, and evaluated T cell responses to concanavalin A (Con A) or keyhole limpet hemocyanin (KLH) by measuring the amount of [3H]thymidine incorporated into DNA. Cells that phagocytized liposomal particles were sorted using flow cytometry and analyzed. Serum anti-KLH antibody was measured after immunizing rats with KLH. Results showed that T cell proliferation in response to Con A or KLH was inhibited from 6 h to 3 days after the liposome injection. Direct cell-to-cell contact was necessary for the suppression. Both inducible nitric-oxide synthase and arginase inhibitors restored T cell proliferation to some degree. The suppression abated 7 days later. Cells that trapped vesicles were responsible for the suppression. Most expressed CD11b/c but lacked class II molecules. However, the primary antibody response to KLH was unaffected. We conclude that the phagocytosis of the large load of liposomal particles by rat CD11b/c+, class II immature monocytes temporarily renders them highly immunosuppressive, but the systemic immune response was unaffected.