[The modulatory role of phospholipids, phosphorylcholine ethers and alkylphosphocholines in signal transduction].

The aim of this review is to provide the molecular evidence as well as the properties and significant role of the platelet activating factor, acetylalkylglycerylic ethers analogs of phosphorylcholines and the alkylphosphocholines, a new class of pharmacophores, in signal transduction processes. These substances are involving in many cellular functions, including immune responses, differentiation, growth control, migration, tumor promotion and cell death. It was established that alkylphosphocholine have inhibitory activities on protein kinase C (PKC) and phospolipase C. Recent data showed that PKC plays an important role in intracellular signalling process and PKC pathway of signal transduction may be involved in cellular differentiation and in the induction of apoptosis. Alkylphosphocholines and their prototype hexadecylphosphocholine (miltefosine) also produce differentiation-inducing effect on hematopoetic cells in vitro and in vivo leading to leuko-and thrombocytosis. It was shown that various PKC isoenzymes regulate the expression of enzymes important for malignant phenotype and PKC suppression by milthefosine may affect tumor invasion and metastasis formation. Miltefosine is able to change immunological reactions to enhance the immune response of interleukin-2-stimulating mononuclear cells, resulting in interferon gamma gene expression and interferon gamma secretion. It has been shown after miltefosine influence a significant maturation of lymphoid tissues and increased numbers of immune cells, which is an additional conformation of miltefosine influence of cell differentiation. It is evident that phosphocholilipids and phosphocholines interact with signal transduction pathways which can lead to alteration of different biological effects.