Document Detail


Identification of a subgroup of myelodysplastic patients with a neutrophil stimulation-signalling defect.
MedLine Citation:
PMID:  7918069     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
f-Met-Leu-Phe-stimulated luminol-enhanced chemiluminescence was found to be repeatedly defective in some MDS patients. This defect was not attributed to myeloperoxidase deficiency, nor to a defect in NADPH oxidase function, because PMA chemiluminescence was found to be normal in these individuals. An arbitrary value of 7 mV (half the mean control value) was chosen to subdivide the group: MDS patients with values < 7 mV had a mean f-Met-Leu-Phe chemiluminescence response of 2.5 +/- 0.5 compared to MDS patients with values > 7 mV who had a mean response of 15.6 +/- 1.6 mV, P < 0.01 (healthy controls 14 +/- 2 mV). The characteristics of the f-Met-Leu-Phe receptor and initial calcium flux results suggested that the receptor itself was normal in number and function in low f-Met-Leu-Phe responders. The rate of superoxide generation, which is calcium-dependent, was also found to be in the normal range in low f-Met-Leu-Phe responders, although total superoxide production was reduced in some of these patients. When MDS neutrophils with a low f-Met-Leu-Phe response were stimulated with PMA, chemiluminescence was normal, suggesting normal activity of the NADPH-oxidase complex. Furthermore, myeloperoxidase activity was reduced in only three out of the 11 low f-Met-Leu-Phe responders. Following priming with GM-CSF, f-Met-Leu-Phe chemiluminescence was 27 +/- 1.6 mV in low f-Met-Leu-Phe responders compared to controls (87.7 +/- 11 mV, P < 0.005). Thus, although responses were improved, they were not as marked as in control neutrophils. These data suggest that a subgroup of MDS patients have a low f-Met-Leu-Phe chemiluminescence response which is not due to a defect in the f-Met-Leu-Phe receptor or oxidase activity, and in the majority of cases MPO activity is normal. Initial patient survival data suggest that these patients may have an increased risk of infective mortality. It is proposed that defective f-Met-Leu-Phe chemiluminescence results from a putative defect in cell-signalling mechanism upstream of PKC, and GM-CSF priming only partially improves responsiveness.
Authors:
G M Lowe; Y Dang; F Watson; S W Edwards; D W Galvani
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  British journal of haematology     Volume:  86     ISSN:  0007-1048     ISO Abbreviation:  Br. J. Haematol.     Publication Date:  1994 Apr 
Date Detail:
Created Date:  1994-11-21     Completed Date:  1994-11-21     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0372544     Medline TA:  Br J Haematol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  761-6     Citation Subset:  IM    
Affiliation:
University Department of Haematology, Royal Liverpool University Hospital.
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MeSH Terms
Descriptor/Qualifier:
Blood Bactericidal Activity
Calcium / blood
Cells, Cultured
Chemiluminescent Measurements
Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
Humans
Myelodysplastic Syndromes / blood*,  mortality
N-Formylmethionine Leucyl-Phenylalanine / pharmacology
Neutrophils / drug effects,  physiology*
Peroxidase / blood
Receptors, Formyl Peptide
Receptors, Immunologic / analysis
Receptors, Peptide / analysis
Superoxides / blood
Tetradecanoylphorbol Acetate / pharmacology
Chemical
Reg. No./Substance:
0/Receptors, Formyl Peptide; 0/Receptors, Immunologic; 0/Receptors, Peptide; 11062-77-4/Superoxides; 16561-29-8/Tetradecanoylphorbol Acetate; 59880-97-6/N-Formylmethionine Leucyl-Phenylalanine; 7440-70-2/Calcium; 83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor; EC 1.11.1.7/Peroxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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