Effects of liposome-encapsulated hemoglobin on human immune system: evaluation in immunodeficient mice reconstituted with human cord blood stem cells.
As preclinical evaluation in animals does not necessarily portray human responses, liposome-encapsulated hemoglobin (LEH), an artificial oxygen carrier, was tested in immunodeficient mice reconstituted with human hematopoietic stem cells (cord blood-transfused NOD/SCID/IL-2R(gammanull)[CB-NOG] mice). Changes in immunocompetent T-cell and B-cell composition in peripheral blood, spleen, and bone marrow were examined 2 and 7 days after 10 mL/kg of intravenous administration of LEH, empty liposome (EL), or saline using immunohistochemical and flow cytometrical techniques in wild-type mice and CB-NOG mice. Responses to intraperitoneal administration of toxic shock syndrome toxin-1 (TSST-1) under the absence or presence of LEH (10 mL/kg) were also determined 4 h and 3 days later in terms of lymphocyte composition and IL-2 plasma level in wild-type as well as CB-NOG mice. When liposome (LEH or EL) was administered to wild-type or CB-NOG mice, the composition of B-cells and T-cells in the spleen or peripheral blood failed to show any consistent or significant changes. The responses to a bacterial antigen (TSST-1) measured by IL-2 production were comparable regardless of the presence or absence of LEH in wild-type as well as in CB-NOG mice. Cellularity, distribution, and maturation of these human cells in peripheral blood, spleen, and bone marrow were comparable among the groups. The results suggest that simple LEH administration may not change immune cellularity, and LEH presence may not largely affect the early T-cell response to bacterial enterotoxins in murine as well as in reconstituted human immune systems.
Kawaguchi
Akira T
AT
Tokai University School of Medicine, Japan. akira@is.icc.u-tokai.ac.jp
Kametani
Yoshie
Y
Kato
Shunichi
S
Furuya
Hiroyuki
H
Tamaoki
Kenichi
K
Habu
Sonoko
S
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001427:Bacterial Toxins / Q000494:pharmacology; D001802:Blood Substitutes / Q000008:administration & dosage* / Q000494:pharmacology; D036101:Cord Blood Stem Cell Transplantation; D004768:Enterotoxins / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D008081:Liposomes / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D023421:Models, Animal; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D018089:Superantigens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D001427:Bacterial Toxins; D001802:Blood Substitutes; D004768:Enterotoxins; D007376:Interleukin-2; D008081:Liposomes; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal