Histamine as a ligand in blood plasma. Part 7. Malate,malonate, maleate and tartrate as adjuvants of zinc to favour histamine tissue diffusion through mixed-ligand coordination.In vitro tests on lymphocyte proliferation

Investigations based on computer simulated distributions of histamine in blood plasma were recently devoted to the assessment of the roles of cysteine, aspartic and glutamic acids as possible adjuvants of zinc to favour histamine tissue diffusion through mixed-ligand coordination. Since all tissues contain at least one of the two enzymes required for the catabolism of histamine, any increase of its tissue diffusion is expected to result in an acceleration of its degradation, which may be of interest for the treatment of anaphylactic disorders. As an extension of these studies, the present paper first reports (i) an experimental investigation of the tendency of four dicarboxylic acids, namely malate, malonate, tartrate and maleate, to mixed-ligand coordination with zinc and histamine, (ii) computer-based potential effects to be expected from the association of these agents to zinc with respect to histamine tissue diffusion. Cell culture studies were then used to test simulation expectations. Two series of experiments involving successively human lymphocytes and a lymphoblastoid cell line (8866) have been carried out, which led to the following conclusions:

1. the hypothesis formerly put forward that cysteine could favour histamine tissue diffusion through mixed-ligand coordination with zinc has been validated on the two cell models,
2. the formerly established suppressive role of histamine versus lymphocyte proliferation has clearly been confirmed,
3. moreover, this suppressive effect has been shown to occur correlatively to histamine uptake by these cells,
4. the four dicarboxylic acids, more especially tartric acid, proved effective as catalysts of the two above processes.

Possible biomedical applications of these results are discussed.