The involvement of CD14 in stimulation of TNF production from peripheral mononuclear cells isolated from PNH patients.
Peripheral blood mononuclear cells (PBMC) from six patients with paroxysmal nocturnal haemoglobinuria (PNH) were analysed by flow cytometry for expression of CD14 and for ability to respond to bacterial lipopolysaccharide and beta 1-4 linked polymannuronic acid by TNF secretion. Expression of cell surface CD14 could not be detected on cells from the PNH patients, whereas the levels of expression of other monocyte antigens, e.g. CD33 and CD13, were comparable to that of cells from healthy subjects. The cells from the patients with PNH responded with secretion of significantly less TNF after stimulation with LPS and polymannuronic acid than mononuclear cells from healthy subjects, suggesting an impaired ability in PNH to respond to bacterial infection by TNF secretion from monocytes. Soluble CD14 appeared to be involved in the residual activation of CD14 negative PBMC, and the sera of these patients contained normal or slightly elevated levels of soluble CD14. After allogeneic bone marrow transplantation in one patient the monocytes expressed CD14 at normal levels and responded normally with respect to their ability to generate TNF upon stimulation.
Sundan
A
A
Institute for Cancer Research and Molecular Biology, University of Trondheim, Norway.
Ryan
L
L
Brinch
L
L
Espevik
T
T
Waage
A
A
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006457:Hemoglobinuria, Paroxysmal / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D018950:Lipopolysaccharide Receptors; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha