In whole blood, LPS, TNF-alpha and GM-CSF increase monocyte uptake of 99mtechnetium stannous colloid but do not affect neutrophil uptake.
BACKGROUND
(99m)Technetium stannous colloid (TcSnC) is used in white cell scanning. It labels neutrophils and monocytes via phagocytosis, with uptake mediated by the phagocytic receptor CD11b/CD18 in neutrophils. Uptake of TcSnC is altered by gram-negative infection, possibly due to the endotoxin component lipopolysaccharide (LPS) or to cytokines released during infection (e.g., TNF-alpha and IFN-gamma). Endotoxemia and increased TNF-alpha levels also occur in inflammatory bowel disease. Another potential confounder in cell labeling is that sepsis patients may be treated with GM-CSF and G-CSF, which alter phagocytic cell function. This study aimed to determine how these factors affect TcSnC cellular uptake.


METHODS
Whole blood from six healthy volunteers was incubated with LPS, TNF-alpha, IFN-gamma, GM-CSF or G-CSF. Samples were then mixed with TcSnC. Blood was separated across density gradients and imaged using a gamma camera. Three radioactive count peaks were observed in each tube: free plasma activity, mononuclear cell uptake and neutrophil uptake.


RESULTS
Compared with controls, significant increases in mononuclear cell uptake were induced by LPS, TNF-alpha and GM-CSF stimulation. It was incidentally noted that exogenous estrogens appear to affect TcSnC labeling and may influence the neutrophil response to stimulation. Neutrophil uptake and plasma activity were not significantly affected. IFN-gamma and G-CSF had no significant effect.


CONCLUSIONS
In whole blood, the effect of LPS on TcSnC monocyte uptake is different to its effect on neutrophils, consistent with previously reported differences in CD11b/CD18 expression. TNF-alpha response parallels LPS response. GM-CSF also increases TcSnC uptake by monocytes. These effects should be considered when using TcSnC for imaging purposes, as they will tend to increase monocyte labeling. Estrogens may also affect TcSnC labeling. Responses to IFN-gamma and G-CSF are consistent with previously reported effects of these cytokines on CD11b/CD18 expression.
Ramsay
Stuart C
SC
Townsville Nuclear Medicine, Mater Hospital, Pimlico, Queensland 4812, Australia. stuart.ramsay1@jcu.edu.au
Maggs
Jacqueline
J
Powell
Kellie
K
Barnes
Jodie
J
Ketheesan
Natkunam
N
D000328:Adult; D002478:Cells, Cultured; D004338:Drug Combinations; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000097:blood / Q000493:pharmacokinetics; D017556:Technetium Compounds / Q000097:blood* / Q000493:pharmacokinetics*; D017971:Tin Compounds / Q000097:blood* / Q000493:pharmacokinetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004338:Drug Combinations; D008070:Lipopolysaccharides; D019275:Radiopharmaceuticals; D017556:Technetium Compounds; D017971:Tin Compounds; D014409:Tumor Necrosis Factor-alpha; C033493:technetium Tc 99m tin colloid; D016178:Granulocyte-Macrophage Colony-Stimulating Factor