Submitted April 21, 2006
Accepted June 7, 2006
Timing of neutrophil tissue repopulation predicts restoration of innate immune protection in a murine bone marrow transplant model
Chrisovalantou Cheretakis, Rolan Leung, Chun Xiang Sun, Yigal Dror, and Michael Glogauer*
University of Toronto, Toronto, ON, Canada
Hospital for Sick Children, Toronto, ON, Canada
* Corresponding author; email: michael.glogauer{at}utoronto.ca.
It has been suggested that neutrophil tissue repopulation following bone marrow transplantation (BMT) serves as an earlier and more relevant marker of susceptibility to infection than circulating neutrophil counts. In a previous study using an oral rinse protocol, we found that oral neutrophil recovery always preceded blood neutrophil engraftment and that the day of oral neutrophil detection served as a predictor of patient susceptibility to infection post-BMT. Consequently, we have developed and validated a mouse BMT model which uses bone marrow transplants containing enhanced green fluorescent protein expressing neutrophils to follow neutrophil tissue repopulation post-BMT. Using this in vivo cell migration model, we assessed the significance of neutrophil tissue recruitment kinetics with neutrophil functionality and in vivo bacterial killing post-BMT. Using the animal model, we have demonstrated that protection against bacterial infection is conferred at the time of neutrophil tissue delivery, which always occurs before neutrophils are detected in the blood. We therefore conclude that neutrophil tissue recovery is an early measure of the restoration of cellular innate immune function post-BMT. This model will help us better understand the factors regulating neutrophil recruitment to the tissues.
