Tumor necrosis factor-alpha production by alveolar macrophages in heart-lung transplant recipients.
Tumor necrosis factor-alpha (TNF alpha) is a cytokine produced by mononuclear cells that amplifies inflammation and modulates expression of Class I and Class II histocompatibility antigens. Because of these properties, this cytokine may exert a central role in both the defense and the rejection of the transplanted lung. Utilizing an ELISA technique, we measured TNF alpha in vivo and in vitro in several compartments of lung transplant recipients and in normal subjects that included serum, bronchoalveolar lavage fluid (BAL), and media conditioned by alveolar macrophages (AM) and by autologous peripheral blood monocytes (PBM). Overall, stimulated production of TNF alpha by AM from lung recipients in vitro was less than that of cells from normal subjects in response to lipopolysaccharide (LPS) challenge, and stimulated production of TNF alpha by AM harvested during conditions of infection or acute and chronic rejection was less than that by cells from healthy lung recipients. AM from normal subjects and allograft recipients produced substantially more TNF alpha than autologous PBM, but release in vitro by PBM from recipients was the same as that from cells of normal subjects who were not immunosuppressed. Thus, systemic immunosuppression does not seem to affect the production of TNF alpha by PBM in vitro, but it may reduce production by AM, indicating different effects of immunosuppression on different compartments of mononuclear cells. This mediator was not detected at elevated levels in serum, and it was undetectable in BAL fluid. We conclude that AM from lung recipients are capable of producing TNF alpha, which would influence the defense and immunogenicity of the allograft.(ABSTRACT TRUNCATED AT 250 WORDS)
Lega
M
M
Department of Oncology, Pittsburgh Cancer Institute, University of Pittsburgh, School of Medicine, Pennsylvania.
Dauber
J H
JH
Urch
S E
SE
Banas
R
R
Whiteside
T L
TL
Griffith
B P
BP
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D016041:Heart-Lung Transplantation / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D012141:Respiratory Tract Infections / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha