Effect of in vivo TNF administration on superoxide production and PKC activity of rat alveolar macrophages.
After the intravenous injection of recombinant human tumor necrosis factor (TNF)-alpha (6.0 x 10(5) U) into rats, phorbol 12-myristate 13-acetate (PMA)-stimulated superoxide anion (O2-) secretion was enhanced in suspensions of alveolar macrophages (AM phi) compared with saline-treated controls. No enhancement of spontaneous, A23187-stimulated, or opsonized zymosan (OPZ)-stimulated O2- release was observed. Intratracheal injection of TNF-alpha (6.0 x 10(5) U) did not result in enhancement of spontaneous or A23187-, OPZ-, or PMA-stimulated O2- release. Although no TNF-alpha was detected in the bronchoalveolar lavage fluid, small quantities of TNF-alpha and/or other mediators secreted by polymorphonuclear leukocytes present in the lung capillaries, veins, and arteries may have leaked into the alveolar compartment and primed AM phi for enhanced PMA-stimulated O2- release. The respiratory burst in macrophages and neutrophils appears to be dependent on the translocation of protein kinase C. We have demonstrated protein kinase C translocation in both TNF-alpha- and saline-treated AM phi on PMA stimulation, although no differences were observed due to TNF-alpha treatment.
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112-1393.
A M
AM
Mayer
R A
RA
Pittner
G E
GE
Lipscomb
J A
JA
Spitzer
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001773:Blood Cells / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007267:Injections; D007275:Injections, Intravenous; D007958:Leukocyte Count / Q000187:drug effects; D008168:Lung / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism*; D009994:Osmolar Concentration; D010100:Oxygen / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014132:Trachea; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000494:pharmacology*; D015054:Zymosan / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D015054:Zymosan; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen