Endogenous PMN-derived reactive oxygen intermediates provide feedback regulation on respiratory burst signal transduction
| Autor: | Alexandre Derevianko, H. Hank Simms, Thomas Graeber, R. D'Amico, Hugh Keeping |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Lipopolysaccharides
Azides Neutrophils Immunology Endogeny GTP-Binding Protein alpha Subunits Gi-Go Second Messenger Systems Antioxidants Feedback Receptors Interleukin-8A Antigens CD Phospholipase D Humans Immunology and Allergy Receptor Peroxidase Respiratory Burst Alanine biology Phospholipase C Superoxide Dismutase Interleukin-8 Receptors Interleukin Cell Biology Catalase Respiratory burst Cell biology Enzyme Activation Biochemistry Type C Phospholipases Myeloperoxidase Second messenger system biology.protein Signal transduction Reactive Oxygen Species Signal Transduction |
| Zdroj: | Journal of Leukocyte Biology. 62:268-276 |
| ISSN: | 1938-3673 0741-5400 |
| DOI: | 10.1002/jlb.62.2.268 |
| Popis: | The role of polymorphonuclear leukocytes (PMN) in stemming systemic infection is executed mainly by the utilization of molecular O2 leading to the production of reactive oxygen intermediates (ROI). PMN-derived ROI also serve as intra- and extracellular second messengers providing both positive and negative feedback on cellular autoregulation. We investigated the effect of endogenous ROI on two signal transducing pathways: the receptor (R)-G-protein-phospholipase D (PLD) and receptor (R)-G-protein-phospholipase C pathways responsible for the subsequent interleukin-8 (IL-8)-induced PMN respiratory burst. Purified human PMN were primed with LPS adhered to plastic surfaces and stimulated with IL-8 with or without the presence of each of five different selective ROI scavengers/antioxidants: DMSO, NaN3, L-alanine, catalase, or superoxide dismutase. Total IL-8 surface receptor expression was assessed by 125I-IL-8 125I-labeled mAbs against IL-8R type A and B binding assays; PLD activation was assessed by measuring formation of phosphatidyl ethanol (PEt) in the presence of ethanol; PLC activation was measured by quantitative conversion of [32P]ATP-labeled phosphatidic acid (PA) into diacylglycerol (DAG); expression of Gα-inhibitory subunit was assessed by SDS-PAGE and immunoblotting with polyclonal Abs against this subunit. Production of O2–, H2O2, HClO, and myeloperoxidase (MPO) in the experimental model was confirmed in a separate set of experiments. The overall impact of antioxidants on each component of the transducing tripartite complex was stimulatory; however, NaN3 and SOD exhibited the most ubiquitous effect with consistent upregulation by NaN3 of IL-8R expression, whereas even trace amounts of externally added authentic MPO significantly down-regulated the functional activity of both effector enzymes. These results demonstrate a multiple site-specific targeting of the signal-transducing complex by endogenous PMN-derived ROI and an overall protective effect of ROI scavengers/antioxidants. |
| Databáze: | OpenAIRE |
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