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Recipient humoral immunity against leukoreduced allogeneic platelets is suppressed by aminoguanidine, a selective inhibitor of inducible nitric oxide synthase

Bang, Annie ; Speck, Edwin R. ; Blanchette, Victor S. ; Freedman, John and Semple, John W. LU (1996) In Blood 88(8). p.2959-2966
Abstract

Leukoreduced allogeneic platelet transfusions have been previously shown to initially stimulate an in vitro cellular cytotoxicity and subsequently induce the formation of immunoglobulin G (IgG) antidonor alloantibodies. To further characterize these responses and determine if they are related, recipient BALB/c H-2(d) mice were treated with aminoguanidine (AMG), a selective inhibitor of inducible nitric oxide synthase (iNOS), and transfused weekly with 2 x 108 C57BL/6 H2b platelets. In control, non-AMG-treated mice, transfusion significantly (P < .01) increased serum levels of interferon-γ (IFN-γ) by day 1 posttransfusion (PT). IFN-γ returned to pretransfusion levels by day 3 PT, and its production was not... (More)

Leukoreduced allogeneic platelet transfusions have been previously shown to initially stimulate an in vitro cellular cytotoxicity and subsequently induce the formation of immunoglobulin G (IgG) antidonor alloantibodies. To further characterize these responses and determine if they are related, recipient BALB/c H-2(d) mice were treated with aminoguanidine (AMG), a selective inhibitor of inducible nitric oxide synthase (iNOS), and transfused weekly with 2 x 108 C57BL/6 H2b platelets. In control, non-AMG-treated mice, transfusion significantly (P < .01) increased serum levels of interferon-γ (IFN-γ) by day 1 posttransfusion (PT). IFN-γ returned to pretransfusion levels by day 3 PT, and its production was not affected by AMG treatment. Serum interleukin-4 (IL-4), on the other hand, was undetectable before and during the transfusion protocol. By day 3 PT, recipient spleen cells could mediate in vitro anti-P815 (auto), anti-EL4 (allo), and anti- R1.1 (third-party MHC) cytotoxicity, and these responses were maximal by day 7 PT. Concurrently, a significant reduction in the in vitro ability of recipient splenocytes to respond to Concanavalin A (ConA) was observed; this was not seen with lipopolysaccharide (LPS) stimulation. Elevated levels of NO2/- were found in the ConA culture supernatants from transfused mice at day 3 PT. Serum antidonor alloantibodies were detected by the fifth platelet transfusion. AMG treatment of recipient mice significantly inhibited the transfusion-induced cytotoxicity and ConA-stimulated NO2/- production, and restored ConA-induced proliferation to normal levels. AMG appeared to selectively inhibit platelet-induced alloantibody production in that it did not affect antibody production induced by transfusions with 106 allogeneic leukocytes or by immunization with a foreign protein antigen, human γ globulin, in adjuvant therapy. These results indicate that an in vivo AMG- sensitive mechanism is essential for recipients to initiate a humoral IgG immune response against allogeneic platelets.

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Contribution to journal
publication status
published
in
Blood
volume
88
issue
8
pages
8 pages
publisher
American Society of Hematology
external identifiers
  • pmid:8874192
  • scopus:0029859178
ISSN
0006-4971
language
English
LU publication?
no
id
dc9d4fb9-54ae-4a85-8790-d952168fcaef
date added to LUP
2019-12-03 10:31:09
date last changed
2024-03-04 09:38:06
@article{dc9d4fb9-54ae-4a85-8790-d952168fcaef,
  abstract     = {{<p>Leukoreduced allogeneic platelet transfusions have been previously shown to initially stimulate an in vitro cellular cytotoxicity and subsequently induce the formation of immunoglobulin G (IgG) antidonor alloantibodies. To further characterize these responses and determine if they are related, recipient BALB/c H-2(d) mice were treated with aminoguanidine (AMG), a selective inhibitor of inducible nitric oxide synthase (iNOS), and transfused weekly with 2 x 10<sup>8</sup> C57BL/6 H2<sup>b</sup> platelets. In control, non-AMG-treated mice, transfusion significantly (P &lt; .01) increased serum levels of interferon-γ (IFN-γ) by day 1 posttransfusion (PT). IFN-γ returned to pretransfusion levels by day 3 PT, and its production was not affected by AMG treatment. Serum interleukin-4 (IL-4), on the other hand, was undetectable before and during the transfusion protocol. By day 3 PT, recipient spleen cells could mediate in vitro anti-P815 (auto), anti-EL4 (allo), and anti- R1.1 (third-party MHC) cytotoxicity, and these responses were maximal by day 7 PT. Concurrently, a significant reduction in the in vitro ability of recipient splenocytes to respond to Concanavalin A (ConA) was observed; this was not seen with lipopolysaccharide (LPS) stimulation. Elevated levels of NO<sub>2</sub>/<sup>-</sup> were found in the ConA culture supernatants from transfused mice at day 3 PT. Serum antidonor alloantibodies were detected by the fifth platelet transfusion. AMG treatment of recipient mice significantly inhibited the transfusion-induced cytotoxicity and ConA-stimulated NO<sub>2</sub>/<sup>-</sup> production, and restored ConA-induced proliferation to normal levels. AMG appeared to selectively inhibit platelet-induced alloantibody production in that it did not affect antibody production induced by transfusions with 10<sup>6</sup> allogeneic leukocytes or by immunization with a foreign protein antigen, human γ globulin, in adjuvant therapy. These results indicate that an in vivo AMG- sensitive mechanism is essential for recipients to initiate a humoral IgG immune response against allogeneic platelets.</p>}},
  author       = {{Bang, Annie and Speck, Edwin R. and Blanchette, Victor S. and Freedman, John and Semple, John W.}},
  issn         = {{0006-4971}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{8}},
  pages        = {{2959--2966}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood}},
  title        = {{Recipient humoral immunity against leukoreduced allogeneic platelets is suppressed by aminoguanidine, a selective inhibitor of inducible nitric oxide synthase}},
  volume       = {{88}},
  year         = {{1996}},
}