In whole blood, LPS, TNF-alpha and GM-CSF increase monocyte uptake of 99mtechnetium stannous colloid but do not affect neutrophil uptake

Ramsay, Stuart C.; Maggs, Jacqueline; Powell, Kellie; Barnes, Jodie; Ketheesan, Natkunam

doi:10.1016/j.nucmedbio.2006.04.002

« Previous Next »Nuclear Medicine and Biology
Volume 33, Issue 5 , Pages 645-651, July 2006

In whole blood, LPS, TNF-alpha and GM-CSF increase monocyte uptake of ^99mtechnetium stannous colloid but do not affect neutrophil uptake

Stuart C. Ramsay
- Townsville Nuclear Medicine, Mater Hospital, Pimlico, Queensland 4812, Australia
- School of Medicine, James Cook University, Townsville, Queensland 4811, Australia
- Corresponding author. Townsville Nuclear Medicine, Mater Hospital, Pimlico, QLD, Australia. Tel.: +61 7 47592800.
Jacqueline Maggs
- Department of Nuclear Medicine, The Townsville Hospital, Townsville, Queensland 4814, Australia
Kellie Powell
- School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811, Australia
- School of Medicine, James Cook University, Townsville, Queensland 4811, Australia
Jodie Barnes
- School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811, Australia
Natkunam Ketheesan
- School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811, Australia
- School of Medicine, James Cook University, Townsville, Queensland 4811, Australia

Received 14 March 2006; received in revised form 4 April 2006; accepted 15 April 2006.

Abstract

Introduction

^99mTechnetium 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.

Keywords: White cell scanning, LPS, TNF-alpha, GM-CSF