Philadelphia chromosome-positive chronic myelogenous leukemia: functional defects in circulating mature neutrophils of untreated and interferon-alpha-treated patients.
This study focuses on possible functional defects of circulating mature neutrophils in chronic phase chronic myelogenous leukemia (CML) and their modulation by interferon-alpha (IFN-alpha). Polymorphonuclear cells (PMN) of seven untreated and nine IFN-alpha-treated patients were evaluated for the following parameters by the following methods: generation of oxygen species, by luminol-dependent chemiluminescence; leukotriene B4 (LTB4) generation, by high-performance liquid chromatography (HPLC); expression of LTB4 and formylmethionyl-leucyl phenylalanine (FMLP) receptor sites, by 3H-binding assay; and GTPase activity, by 32P-gamma-GTP. Compared to normal controls, reduced values were obtained in treated and untreated CML for most parameters studied. Therapy with IFN-alpha resulted in significantly diminished values for oxygen species (NaF stimulation) and LTB4 (FMLP stimulation) generation, as well as FMLP receptor expression as compared to untreated CML. We conclude that alterations at the level of oxygen species production, mediator generation, receptor expression, and transmembrane signaling are involved in functional defects of circulating mature neutrophils from CML patients. IFN-alpha seems to enhance some of these functional defects, but the clinical relevance of these findings has be elucidated.
Kasimir-Bauer
S
S
Department of Medical Microbiology and Immunology, Ruhr University of Bochum, Germany.
Ottinger
H
H
Brittinger
G
G
König
W
W
D000328:Adult; D000368:Aged; D002462:Cell Membrane / Q000201:enzymology / Q000502:physiology / Q000648:ultrastructure; D002851:Chromatography, High Pressure Liquid; D005260:Female; D020558:GTP Phosphohydrolases / Q000032:analysis / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D007975:Leukotriene B4 / Q000378:metabolism; D008163:Luminescent Measurements; D008165:Luminol; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D017382:Reactive Oxygen Species / Q000378:metabolism; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000032:analysis / Q000378:metabolism; D018077:Receptors, Leukotriene / Q000032:analysis / Q000378:metabolism; D018000:Receptors, Peptide / Q000032:analysis / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D016898:Interferon-alpha; D017382:Reactive Oxygen Species; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018077:Receptors, Leukotriene; D018000:Receptors, Peptide; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D008165:Luminol; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins