Stimulation of neutrophils by tumor necrosis factor

• Published in: The Journal of immunology (1950) Vol. 136; no. 11; pp. 4220 - 4225
• Main Authors: Klebanoff, SJ, Vadas, MA, Harlan, JM, Sparks, LH, Gamble, JR, Agosti, JM, Waltersdorph, AM
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 01.06.1986; American Association of Immunologists
• Subjects: Biological and medical sciences; Cytoplasmic Granules - enzymology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glycoproteins - pharmacology; Humans; Hydrogen Peroxide - biosynthesis; Immunobiology; Iodine Radioisotopes - metabolism; L-Lactate Dehydrogenase - metabolism; Modulation of the immune response (stimulation, suppression); Neutrophils - enzymology; Neutrophils - metabolism; Neutrophils - physiology; Peroxidase - metabolism; Phagocytosis - drug effects; Recombinant Proteins - pharmacology; Tumor Necrosis Factor-alpha; Zymosan - pharmacology; Human; Leucocyte function; Tumor necrosis factor; Leukocyte; Neutrophile; Degranulation; Activation; Respiratory burst; Biological activity; Phagocytosis
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.136.11.4220

Human recombinant tumor necrosis factor (TNF) was shown to be a weak direct stimulus of the neutrophil respiratory burst and degranulation. The stimulation, as measured by iodination, H2O2 production, and lysozyme release, was considerably increased by the presence of unopsonized zymosan in the reaction mixture, an effect which was associated with the increased ingestion of the zymosan. TNF does not act as an opsonin but, rather, reacts with the neutrophil to increase its phagocytic activity. TNF-dependent phagocytosis, as measured indirectly by iodination, is inhibited by monoclonal antibodies (Mab) 60.1 and 60.3, which recognize different epitopes on the C3bi receptor/adherence-promoting surface glycoprotein of neutrophils. Other neutrophil stimulants, namely N-formyl-methionyl-leucyl-phenylalanine, the Ca2+ ionophore A23187, and phorbol myristic acetate, also increase iodination in the presence of zymosan; as with TNF, the effect of these stimulants is inhibited by Mab 60.1 and 60.3, whereas, in contrast to that of TNF, their stimulation of iodination is unaffected by an Mab directed against TNF. TNF may be a natural stimulant of neutrophils which promotes adherence to endothelial cells and to particles, leading to increased phagocytosis, respiratory burst activity, and degranulation.