Neutrophil-macrophage interaction: a paradigm for chronic inflammation.
Autoimmune diseases, such as rheumatoid arthritis and inflammatory bowel disease are characterized by chronic inflammatory responses resulting in tissue damage. These diseases have a number of common denominators including: abnormal cytokine expression, aberrant antigen-antibody complexes, T cell anomalies, and increased numbers of neutrophils and macrophages. We propose that the interaction between neutrophils and macrophages induces a state of chronic inflammation which contributes to the disease state. One of the central players in this scenario is myeloperoxidase (MyPo). This enzyme functions in the 'cytotoxic triad' and is involved in cell killing. Studies done by the present investigators have known that MyPo, which is released from neutrophils, induces macrophages to secrete interleukin-1, interferon alpha beta and tumor necrosis factor alpha. Furthermore, our studies have suggested a major immunoregulatory role of this enzyme. We propose that the release of MyPo from neutrophils and subsequent binding to macrophages initiates a cascade of events which enhance the production of reactive oxygen intermediates and cytokine expression resulting in the chronic inflammatory state associated with autoimmune diseases.
Lefkowitz
D L
DL
Department of Biological Sciences, Texas Tech University, Lubbock, USA.
Mills
K
K
Lefkowitz
S S
SS
Bollen
A
A
Moguilevsky
N
N
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D001327:Autoimmune Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D016207:Cytokines; D017382:Reactive Oxygen Species; D009195:Peroxidase