Granulocyte Kinetics in Health and Disease

The innate immune system is indispensable for defence against pathogens. Yet, little is known about the behaviour of innate immune cells in the body. For example, there is little consensus regarding the circulatory lifespans of neutrophils, eosinophils and basophils in healthy individuals. For the lifespans and behaviour of these cells in tissues and in acute or chronic inflammation, no information is available at all. Without this knowledge, it is very difficult to interpret and design clinical trial targeting these cells.
Therefore, we estimated the circulatory lifespans of neutrophils, eosinophils and basophils in healthy controls by use of in vivo deuterium labelling. This method allows labelling of these cells without any toxic side-effects or manipulation. Hereby, we estimate that these cells remain longer in the bloodstream than previously anticipated.
In addition to estimating circulatory lifespans, this technique can also be used to gain information of the developmental relationships between immune cells. For example, three different subsets of monocytes are recognised in the circulation, but it is uncertain whether these three subsets represent a different maturation stage of the same cell or whether they are all three different cell developing separately in the bone marrow. By combining deuterium labelling results with mathematical modelling, we show that the three monocyte subsets can be different maturation stages of the same cell, but only if part of this process takes place outside of the bloodstream and if only few cells mature into all three different subsets.