Histamine and the Blood

Granulocyte-macrophage colony stimulating factor (GM-CSF) stimulates the in vitro proliferation and differentiation of granulocytic and macrophage cells. This regulator is now known to act at other levels of hemopoietic regulation. The heterogeneity of GM-CSFs is not only related to the tissue of origin and the in vitro production method, but also to functional subclasses of the molecule that have distinct biologic specificities. Most adult mouse organs produce GM-CSF (mol wt 23,000), but a macrophage (M)-CSF has been detected in fetal conditioned medium (CM) and isolated from L-cell CM. Murine endotoxin serum appears to contain a M-CSF, GM-CSF, and G-CSF, the last of which cofractionates with a differentiation factor active on leukemic cells. Human GM-CSFs, G-CSF, and EO-CSFs active on human cells have been detected in a variety of CM, but as yet none have been purified. Again, there are subclasses of progenitor cells that respond to particular forms of human active CSFs. GM-CSF isolated from mouse lung CM stimulates multipotential progenitor cells, the initial proliferatin of progenitors in the erythroid, eosinophil, and megakaryocyte series, as well as mature cells in the GM series. While GM-CSF is also able to stimulate the differentiation of myeloid leukemic cells, other factors appear to be more potent in this respect. Information on the regulation of GM-CSF production, on the modulators of its action on specific target cells, and on its role in vivo will be required before the physiologic function of this molecule can be properly assessed.

Platelet-activating factor (PAF-acether), an inflammatory mediator with a wide range of biological activities including neutrophil aggregation and chemotaxis, was studied for its effect on human eosinophil locomotion (chemotaxis and chemokinesis). Human eosinophils (25-95% purity) were obtained from donors with a variety of diseases associated with hypereosinophilia. PAF-acether elicited directional locomotion of eosinophils, in a time- and dose-dependent fashion, at concentrations from 10(-5) to 10(-8) M; lyso-PAF had minimal activity over the same dose range. Compared with PAF-acether, the eosinophil locomotory responsiveness of leukotriene B4 (LTB4), histamine, and the valyl- and alanyl-eosinophil chemotactic factor of anaphylaxis (ECF-A) tetrapeptides was negligible. Conversely, neutrophil responsiveness to PAF-acether (optimum 10(-6) M) was comparable in effect to LTB4 (optimum dose 10(-8) M). It was shown that PAF-acether elicited both chemotaxis and chemokinesis of eosinophils. Comparison of normal density and light density eosinophils revealed no qualitative difference in the response to PAF-acether and the other chemoattractants, although the light density cells seemed to demonstrate a greater degree of locomotion to PAF-acether and LTB4. Thus, PAF-acether appears to be a potent eosinophilotactic agent which may play a role in inflammatory reactions characterized by eosinophil infiltration.