The role of blood platelets in nucleoside metabolism: regulation of megakaryocyte development and platelet production.

In higher vertebrates, different types of blood cells develop from common precursors. Mammals are unique in possessing two types of blood cells--erythrocytes and platelets--which lack nuclei. Although platelets display consistent and easily-recognisable morphological and ultrastructural characteristics and show extreme metabolic and functional versatility, they are not true cells, being produced by fragmentation of giant polyploid precursors called megakaryocytes. At present, the physiological mechanisms which regulate megakaryocyte development and platelet production are not well understood. Platelets are actively involved in metabolism of purine derivatives and a significant platelet role in pyrimidine metabolism has also been demonstrated (see previous papers). Here an attempt is made to integrate information about platelet involvement in nucleic acid precursor metabolism with current concepts of haematopoiesis, particularly megakaryocyte development and platelet production. It is concluded (i) that megakaryocytic cells are immediate descendents of haematopoietic stem cells which have become polyploid as a result of genetic damage or metabolic imbalances, (ii) megakaryocytes and platelets are the ultimate regulators of stem cell development because they control the availability of thymidine and (iii) that the production of megakaryocytes and platelets is a physiological safety mechanism which prevents fixation of genetic damage and protects other cells from potentially cytotoxic and genotoxic stimuli.