Hemopoietic cells perform many vital functions in the maintenance of homeostasis
and integrity of the body. These functions include, among others, the transport of oxygen
by erythrocytes, and the initiation of blood clotting by thrombocytes at sites of injury.
Furthermore, hemopoietic cells are the primary effector cells in the defense against
micro-organisms and tumor cells. This defense is mainly carried out by two different cell
types: lymphocytes and phagocytes. The distinction between these cell types is, among
other things, based upon the different mechanisms that lymphocytes and phagocytes use
to recognize foreign material. Lymphocytes recognize invading substances by highly
specific antigen receptor molecules which are different and specific for each antigen.
Mononuclear and polymorphonuclear phagocytes, on the other hand, discern their
foreign targets by receptor molecules with much broader specificity, such as lectin-like
receptors recognizing carbohydrate moieties.
From an evolutionary point of view, phagocytes are the most 'ancient' cells in host
defense. All multicellular animals contain amoeboid phagocytic cells; in some
invertebrates such cells are even the only blood cells present. In general, increasing
evolutionary ancientry coincides with increasing phenotypical diversity. The heterogeneity
among phagocytes, and especially among the mammalian mononuclear phagocytes,
clearly demonstrates the validity of this general rule.
In this thesis, an analysis is presented of the phenotypical differentiation of murine
mononuclear phagocytes, i.e. macrophages and their precursors. The term 'differentiation'
in this context includes both the process of maturation and of diversification.
It should be realized, however, that the term 'differentiation' is also generally used as
equivalent to maturation only.
In the next section an introductory overview is given of our current knowledge of
macrophage differentiation. The literature cited in this overview primarily deals with
studies performed with mice as experimental animals, since the subsequent chapters
describe results of experimental studies using murine cells