The loss of susceptibility to apoptosis in exudated tissue neutrophils is associated with their nuclear factor-κB activation

• Published in: European journal of pharmacology Vol. 433; no. 1; pp. 17 - 27
• Main Authors: Hotta, Koichi, Niwa, Masayuki, Hara, Akira, Ohno, Takatoshi, Wang, Xiaodan, Matsuno, Hiroyuki, Kozawa, Osamu, Ito, Hidenori, Kato, Kanefusa, Otsuka, Takanobu, Matsui, Nobuo, Uematsu, Toshihiko
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 14.12.2001; Elsevier
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Caspase 3; Caspases - metabolism; circulating blood; Cyclophosphamide - pharmacology; DNA Fragmentation; Enzyme Activation; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; Inflammation; Miscellaneous; Molecular and cellular biology; Neutrophil; Neutrophils - drug effects; Neutrophils - physiology; NF-kappa B - physiology; Regulatory factors and their cellular receptors; Superoxides - metabolism; tissue; Transcription factor; Tumor Necrosis Factor-alpha - pharmacology; Transcription factor; Neutrophil; Apoptosis; Human; Immunopathology; Biological fluid; Healthy subject; Diseases of the osteoarticular system; Tissue specificity; Autoimmune disease; Inflammatory joint disease; Cellular immunity; Inflammation; In vitro; Biological activity; Blood; Synovial fluid; Chronic; Cell death; Rheumatoid arthritis; Defense mechanism; Transcription factor NFκB; Mechanism of action; Saliva; Tumor necrosis factor α
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(01)01480-7

Tissue neutrophils, human salivary neutrophils donated from healthy subjects and synovial fluid neutrophils collected from patients with rheumatoid arthritis were compared with circulating blood neutrophils. Concomitant treatment of circulating blood neutrophils with tumor necrosis factor-α (TNF-α) and cycloheximide induced neutrophil apoptosis, whereas the same treatment failed to induce significant apoptosis in salivary and synovial fluid neutrophils. Caspase-3 activation by TNF-α was observed in these tissue neutrophils, although its activity was significantly weaker than that in circulating blood neutrophils. In circulating blood neutrophils, TNF-α induced activation of nuclear factor-κB (NF-κB), whereas, in tissue neutrophils, NF-κB had been already activated without any stimulation, and no further activation was induced by the treatment with TNF-α. Furthermore, while pretreatment of neutrophils with an NF-κB inhibitor produced typical apoptotic changes in circulating blood neutrophils, this inhibitor did not produce any morphological apoptotic changes induced by TNF-α in tissue neutrophils. These results indicate that neutrophils undergo marked functional changes such as altered sensitivity to apoptosis-inducing stimuli in association with their exudation from blood into tissue, and that NF-κB activation is involved in the acquisition of resistance to TNF-α-induced apoptosis.