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.