Further studies of the defective stimulus-response coupling for the oxidative burst in neutrophils in polycythemia vera.
We have previously reported that the chemiluminescence (CL) response of neutrophils (PMN) from patients with polycythemia vera (PV) was abnormally low when induced by surface receptor-dependent stimuli, fMLP and leukotriene B4, but normal when elicited by phorbol myristate acetate (PMA). This study documents that this discrepancy of the CL response to fMLP and PMA remained over a wide range of stimuli concentrations, was not due to iron-deficient PV cells and was also observed with the nitroblue tetrazolium assay. Moreover, another surface receptor-dependent agonist, platelet-activating factor, conferred a significantly lower CL response in PV PMN relative to controls. Treatment with alpha interferon or GM-CSF, to increase fMLP receptors, resulted in a similar enhancement of fMLP-induced CL in PV and controls. CL was normal when induced by a number of non-surface receptor-dependent stimuli. Release of lactoferrin in response to fMLP (and PMA) was normal (as was previously reported fMLP-induced chemotaxis and adherence). Thus, this defect is highly specific for oxidative metabolism, and localized to discrete step(s) of the stimulus-response coupling for fMLP, leukotriene B4 and PAF, but conceivably not due to impairment of the dynamic interaction of fMLP with its receptor.
Samuelsson
J
J
Department of Medicine 3, Stockholm Söder Hospital, Sweden.
Berg
A
A
D000368:Aged; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000494:pharmacology; D007781:Lactoferrin / Q000097:blood; D008163:Luminescent Measurements; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011087:Polycythemia Vera / Q000097:blood*; D012016:Reference Values; D016897:Respiratory Burst / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016898:Interferon-alpha; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007781:Lactoferrin; D013755:Tetradecanoylphorbol Acetate