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Sep 16: Determination of the lifespan of granulocytes

The lifespan of the neutrophilic granulocyte is at least 2 days. This is much longer that what has been described in the scientific literature (usually approx. 1 day). This is the result of innovative studies on human granulocyte kinetics with deuterium-labelled cells, performed in the PhD-project of Marwan Hassani.

The development, differentiation and maturation of granulocytes has been extensively studied. However, the kinetics (or lifespan) of granulocytes (both neutrophils and eosinophils) are incompletely understood. In recent years, new research methods to investigate human immune cells kinetics in vivo have become available, which has sparked a debate on the circulatory lifespan of the human neutrophil. It also has been shown that the kinetics of eosinophils can be influenced by certain drugs. In this thesis, Marwan Hassani (Center for Translational Immunology and Department of Respiratory Medicine, UMC Utrecht) reports on several studies, in which the lifespan of various white blood cells in the human body were investigated. Two of his findings are highlighted below.

Life span of neutrophils

Hassani studied the kinetics of neutrophils, using bone marrow samples, with help of deuterium (2H)-labelled glucose in 12 healthy volunteers. He concluded with some certainty that neutrophils lives longer than initially thought. The investigators believe that these cells, regardless of the compartment they reside in, can survive for at least 2 days. This is at least 1 day longer than previously thought. He also found that neutrophils that enter the circulation first from the bone marrow, are also the first ones to be degraded. These findings may be important for our understanding of a number of syndromes in which these cells play an essential role.

Eosinophil production rate

The study also indicated that IL-5 (a protein important for eosinophil granulocytes) probably only plays a role in the increase of production of eosinophils. Without IL-5, eosinophils are still produced, but the body is not able to increase this production when necessary. This is important as it helps us understand why mepolizumab may or may not work in some patients with asthma. It also helps to understand any side effects.

Granulocytes

Granulocytes are a type of white blood cells (leukocytes) that are characterized by the large number and chemical makeup of the granules occurring within the cytoplasm. They are the most numerous of the white cells and are approximately 12–15 µm in diameter, making them larger than erythrocytes. They have a multilobed nucleus and are important mediators of the inflammatory response. There are three types of granulocytes: neutrophils, eosinophils, and basophils. They are continuously produced from stem cells in the bone marrow. Granulocytes are mobile and are attracted to foreign materials by chemical signals, which are produced by invading microorganisms, damaged tissues, or by the interaction between microbes and plasma proteins.

PhD defense

Marwan Hassani (1988, Baghdad, Iraq) received his PhD on September 14, 2020 at Utrecht University. The title of his thesis was “Another look at human granulocyte kinetics”. Supervisors was prof. dr. Leo Koenderman (Department of Respiratory Medicine, UMC Utrecht). Marwan Hassani works at the St. Antonius Hospital in Nieuwegein as a registrar in internal medicine.