ROLE OF PASSENGER LEUKOCYTES IN ALLOGRAFT-REJECTION - EFFECT OF DEPLETION OF DONOR ALVEOLAR MACROPHAGES ON THE LOCAL PRODUCTION OF TNF-ALPHA, T-HELPER-1 T HELPER-2 CYTOKINES, IGG SUBCLASSES, AND PATHOLOGY IN ARAT MODEL OF LUNG TRANSPLANTATION/

Acute lung allograft rejection is believed to be initiated by passenge r leukocytes, such as alveolar macrophages (AM), in the donor organ, w hich release TNF-alpha, and present alloantigens to host lymphocytes, leading to up-regulated Th1 cellular and humoral immunity. However, th e role of donor AM in local TNF-alpha synthesis, and their ability to induce local Th1 cellular and humoral immunity have not been evaluated , By depleting Brown Norway (BN, RT1(n)) rat lung allografts of AM bef ore transplantation into Lewis rat (LEW, RT1(1)) recipients, the curre nt study determined the role of donor AM in inducing the production of TNF-alpha, IFN-gamma (Th1 cytokine), IL-4 (Th2 cytokine), IgG subtype s, and rejection pathology in the allograft, The data show that compar ed with untreated BN allografts, pretransplant depletion of donor lung AM resulted in significantly less TNF-alpha, and IFN-gamma production in allograft bronchoalveolar lavage fluid with variable effects on lo cal IL-4 production, Depletion of AM in the donor lung before transpla ntation affected the local production of several IgG subclasses, Howev er, pretransplant depletion of donor AM had no effect on the developme nt of the pathology of severe acute rejection, These data show that do nor AM have a central role in the local synthesis of TNF-alpha and ind uce the production of IFN-gamma and IgG subtypes, locally, during acut e lung allograft rejection, However, depletion of AM before transplant ation does not prevent the development of severe acute rejection in BN rat lungs transplanted into LEW recipients.