title: Platelet-activating factor plays a role in the mechanism of major histocompatibility complex in T lymphocytes.
abstract: In recent studies, using a swine model of single lung transplantation, we demonstrated that IRI alone increased MHC II expression in the host's peripheral T lymphocytes. The inhibition of increased MHC II expression with TCV-309, a specific platelet-activating factor (PAF) antagonist suggested that PAF might play a role in the mechanism of increased MHC II expression. The purpose of the current study was two fold: 1) to investigate the mechanism of PAF-induced increased expression of MHC II in T lymphocytes, 2) to determine whether a specific PAF-antagonist, TCV-309, is capable of inhibiting the increased expression in an in vitro system. This study was subdivided, using four in vitro conditions: 1) purified resting T cells, 2) purified proliferating T cells, 3) PBL treated with PAF, and 4) PBL preincubated with TCV-309 and treated with PAF. The level of MHC II on T cells were measured by two color flow cytometry analysis (swine anti-CD3, MHC II-DR-(beta)antibodies). Both MHC II intensity and the number of CD3+MHC+ T cells did not change in resting purified T cells once treated with PAF, Furthermore, MHC II intensity did not change in purified proliferating T cells treated with PAF. The number of CD3+MHC+ T cells, however, increased significantly (p<0.05) from day 1 to day 4 as compared with pre-treatment value (day 0) for purified proliferating T cells. Treatment of PBL with PAF (10(-7)M) resulted in a significant (p<0.05) increase in MHC II expression from day 2 to day 4 post-treatment. The number of CD3+MHC+ T cells in PBL, however, did not change significantly upon treatment with PAF. The results of this study indicated that PAF did not have a direct effect on increased MHC II expression in resting or proliferating purified T lymphocytes. However, the mechanism of PAF-induced increased expression of MHC II in T cells may be via an indirect pathway involving accessory cells. TCV-309, a specific PAF receptor antagonist, is capable of inhibiting this PAF-induced increased expression of MHC II in T cells.
authors.affiliation: Department of Surgery, University of British Columbia, Vancouver Hospital and Health Sciences Centre, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Nikbakht-Sangari
authors.forename: A K
authors.initials: AK
authors.lastname: Qayumi
authors.forename: P
authors.initials: P
authors.lastname: Keown
authors.forename: V
authors.initials: V
authors.lastname: Duronio
authors.forename: K
authors.initials: K
authors.lastname: Horley
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D016040:Lung Transplantation / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D010835:Phytohemagglutinins / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000494:pharmacology; D013552:Swine; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D044005:Tetrahydroisoquinolines
chemical_list: D017252:CD3 Complex; D000949:Histocompatibility Antigens Class II; D007546:Isoquinolines; D010835:Phytohemagglutinins; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011726:Pyridinium Compounds; D044005:Tetrahydroisoquinolines; C067430:TCV 309