The role of inflammatory mediators in the mechanism of the host immune response induced by ischemia-reperfusion injury.
Our previous study suggested that inflammatory mediators released due to IRI lead to host's immune response by upregulating MHC II in the host's peripheral T lymphocytes. This study hypothesized the role of platelet-activating factor (PAF) in the mechanism of induced MHC II upregulation due to IRI on peripheral T lymphocytes. The objectives of this study were to investigate the role of PAF in the induction of host immune reactivity and the protective effect of PAF-antagonist TCV-309 in combination with prostaglandin E1 (PGE1) against the host's immune response caused by IRI. Thirty female domestic swine were divided into three groups. Group A (6 donors, 6 recipients) had no pharmacological intervention. Group B (6 donors, 6 recipients) was the experimental group treated with TCV-309 + PGE1. Group C underwent sham operation. The ex vivo preservation time for groups A and B was 4 hr at 4 degrees C. To detect the changes in MHC II expression on T cells due to IRI, blood samples were collected before reperfusion (baseline level), 1, 2, and 3 days post-reperfusion. Two-colour flow cytometry analysis (FACS) was used to study MHC II-DR-beta expression in peripheral T lymphocytes. Swine anti-MHC II and anti-CD3 antibodies were used for this purpose. The FACS analyses demonstrated that in group A, there was a significant increase (p < 0.05) in MHC II intensity on peripheral T lymphocytes on day 2 post-reperfusion. By the third day post-reperfusion, MHC intensity had a tendency to decrease but did not reached the baseline level. In group B and C, however, there was no significant change in the level of MHC II in T lymphocytes at any of the post-reperfusion times. In group A, the number of CD3+MHC+ T lymphocytes significantly decreased (p < 0.05) by one day post-reperfusion and remained at this level until the third day post-reperfusion. In groups B and C, no significant change in the number of CD3+MHC+ T cells was observed. The results of this study suggested that the release of inflammatory mediators (e.g. PAF) due to IRI played a role in the mechanism of IRI-induced host's immune response. The results also suggested that the combination of TCV-309 + PGE1 could reduce this immune response.
Nikbakht-Sangari
M
M
Department of Surgery, Vancouver Hospital, BC, Canada.
Qayumi
A K
AK
Keown
P A
PA
D000527:Alprostadil / Q000008:administration & dosage; D000818:Animals; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D018836:Inflammation Mediators / Q000502:physiology*; D007262:Infusions, Intravenous; D007546:Isoquinolines / Q000494:pharmacology / Q000627:therapeutic use; D010972:Platelet Activating Factor / Q000502:physiology; D011726:Pyridinium Compounds / Q000494:pharmacology / Q000627:therapeutic use; D012044:Regression Analysis; D015427:Reperfusion Injury / Q000276:immunology* / Q000378:metabolism; D013552:Swine; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism; D044005:Tetrahydroisoquinolines; D015854:Up-Regulation / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D018836:Inflammation Mediators; D007546:Isoquinolines; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; D044005:Tetrahydroisoquinolines; D000527:Alprostadil; C067430:TCV 309