Linked Life Data

14636244

Source:http://linkedlifedata.com/resource/pubmed/id/14636244

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-11-25
pubmed:abstractText
Chronic granulomatous disease is an inherited disorder associated with a defect in phagocytic cell oxidative metabolism resulting in ineffective microbicidal activity. Consequently, patients with chronic granulomatous disease suffer from recurrent infections. Published data show that besides the failure to produce superoxide and its derivatives, other functional problems can also be found in chronic granulomatous disease-mutant cells. Since in innate immune responses other mediators, such as cytokines, also play an important role, we hypothesized that there may be a disturbance in cytokine production by chronic granulomatous disease-mutant cells as well. To prove this hypothesis, the production of tumour necrosis factor-alpha, an important proinflammatory cytokine, was determined by enzyme-linked immunosorbent assay in wild-type and chronic granulomatous disease-mutant myelomonoblastic PLB-985 cells in their immature, granulocytic and monocytic/macrophage differentiated forms. Tumour necrosis factor-alpha production was induced with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (100 nmol/L), lipopolysaccharide (10 micro g/mL), opsonized zymosan (100 micro g/mL) or phorbol 12-myristate 13-acetate (100 nmol/L) for 24 h. We could demonstrate that: (i) there were marked differences in tumour necrosis factor-alpha production only in the differentiated forms of both wild-type and chronic granulomatous disease-mutant cells, while there were no differences in the case of their immature counterparts; (ii) only chronic granulomatous disease-mutant cells retained sensitivity to phorbol 12-myristate 13-acetate both in their granulocytic and monocytic forms, although phorbol 12-myristate 13-acetate responsiveness was a characteristic of both types of immature cells; (iii) the granulocytic form of wild-type cells produced tumour necrosis factor-alpha after opsonized zymosan stimulation, but such a response was not observed in cells originating from the chronic granulomatous disease-mutant cell line; (iv) with the monocytic forms, significantly higher tumour necrosis factor-alpha production could be induced by lipopolysaccharide in the wild-type cells than in the chronic granulomatous disease-mutant cells, although there was no difference in their lipopolysaccharide receptor CD14 expression. In summary, these data show an altered inducibility of tumour necrosis factor-alpha production by chronic granulomatous disease-mutant cells. Our observations suggest a further defect in differentiated chronic granulomatous disease-mutant cells in addition to the known defect in reduced nicotinamide adenine dinucleotide phosphate oxidase, which may contribute to the development of susceptibility to infections in people with chronic granulomatous disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0818-9641
pubmed:author
pubmed:issnType
Print
pubmed:volume
81
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
472-9
pubmed:meshHeading
pubmed-meshheading:14636244-Antigens, CD14, pubmed-meshheading:14636244-Cell Differentiation, pubmed-meshheading:14636244-Cell Line, Tumor, pubmed-meshheading:14636244-Cells, Cultured, pubmed-meshheading:14636244-Granulocytes, pubmed-meshheading:14636244-Granulomatous Disease, Chronic, pubmed-meshheading:14636244-Humans, pubmed-meshheading:14636244-Lipopolysaccharides, pubmed-meshheading:14636244-Macrophages, pubmed-meshheading:14636244-Monocytes, pubmed-meshheading:14636244-Mutation, pubmed-meshheading:14636244-N-Formylmethionine Leucyl-Phenylalanine, pubmed-meshheading:14636244-Receptors, Cell Surface, pubmed-meshheading:14636244-Receptors, Complement 3b, pubmed-meshheading:14636244-Receptors, IgG, pubmed-meshheading:14636244-Tetradecanoylphorbol Acetate, pubmed-meshheading:14636244-Tumor Necrosis Factor-alpha, pubmed-meshheading:14636244-Zymosan
pubmed:year
2003
pubmed:articleTitle
The inducibility of TNF-alpha production is different in the granulocytic and monocytic differentiated forms of wild type and CGD-mutant PLB-985 cells.
pubmed:affiliation
Department of Pharmacology, Institute of Experimental Medicine, National Medical Centre, Budapest, Hungary.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't