Hypochlorous acid activates tyrosine phosphorylation signal pathways leading to calcium signaling and TNFalpha production.
Hypochlorous acid is an important oxidizing agent produced by neutrophils to aid in defense against pathogens. Although hypochlorous acid is known to cause tissue damage due to its cytotoxicity, the effect of this oxidizing agent on signal transduction by cells of the immune system and its effects on their responses are not well understood. In this study, hypochlorous acid was found to induce cellular tyrosine phosphorylation in both T and B lymphocytes, activate the ZAP-70 tyrosine kinase, and induce cellular calcium signaling in a tyrosine kinase-dependent manner. These signaling events also occurred in T cell lines that did not express the T-cell receptor, indicating the ability of hypochlorous acid to bypass normal receptor control. Hypochlorous acid induced tumor necrosis factor-alpha production in peripheral blood mononuclear cells in a tyrosine kinase-dependent manner. These results suggest that hypochlorous acid may contribute to inflammatory responses by activating signal pathways in cells of the immune system.
Schieven
Gary L
GL
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA. gary.schieven@bms.com
de Fex
Henry
H
Stephenson
Linda
L
D020013:Calcium Signaling / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006997:Hypochlorous Acid / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016877:Oxidants / Q000494:pharmacology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D051746:ZAP-70 Protein-Tyrosine Kinase
D016207:Cytokines; D004791:Enzyme Inhibitors; D016877:Oxidants; D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha; D014443:Tyrosine; D006997:Hypochlorous Acid; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human