The role of lymphocyte production and migration in the lymphopenia caused by 2-acetyl-4-tetrahydroxybutyl imidazole. 1992

S J Gobin, and R F Legg, and A J Paine
DH Department of Toxicology, St. Bartholomew's Hospital Medical College, London, U.K.

2-Acetyl-4-tetrahydroxybutyl imidazole (THI), a component of the food colouring ammonia caramel, has been shown to produce a profound and rapid lymphopenia in peripheral blood in the rat. In order to investigate whether the cause of the lymphopenia was due to the reduced production and influx in the circulation, redistribution of lymphocytes into other lymphoid compartments or an increased cell death, THI (1 mg/kg/day) was given in the drinking water for up to 14 days to F344 rats. A profound depletion of lymphocytes after already 1 day was only found in the blood compartment, whereas no such marked and rapid changes were found in the cellularity of other lymphoid compartments. The proportion and absolute number of DNA-synthesizing cells in each lymphoid organ was quantified using an antibody directed against incorporated 5-bromo-2'-deoxyuridine (BrdU), 1 h after a single BrdU injection. Additionally, enumeration and localization of BrdU+ cells was determined at later time points after a single BrdU injection by flow cytometry and immunocytochemistry, in order to examine the distribution and localization of recently formed (BrdU+) lymphocytes. THI treatment had no effect on the proliferation rate and the distribution of newly formed (BrdU+) cells in the lymphoid organs. However, migration studies revealed that THI treatment resulted in an increased percentage of fluorescein-labelled peripheral blood lymphocytes found in the spleen and bone marrow and a decreased percentage in the cervical and mesenteric lymph nodes, 24 h after injection. Collectively these results indicate that the lymphopenia in the peripheral blood compartment after THI treatment, is caused by a rapid sequestration of lymphocytes into the spleen and bone marrow rather than by a reduced lymphocyte production and release into the periphery. The fact that THI also caused lymphopenia in splenectomized rats, indicates that the spleen does not play an active part in the change in migrational behaviour of lymphocytes after THI treatment. Finally, as there was no increase in the absolute number of lymphocytes found in the spleen or bone marrow it seems they are rapidly degraded.

UI MeSH Term Description Entries
D007093 Imidazoles Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008214 Lymphocytes White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS. Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D008231 Lymphopenia Reduction in the number of lymphocytes. Lymphocytopenia,Lymphocytopenias,Lymphopenias
D008297 Male Males
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002465 Cell Movement The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell. Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D005505 Food Coloring Agents Natural or synthetic dyes used as coloring agents in processed foods. Coloring Agents, Food,Food Colorants,Agents, Food Coloring,Colorants, Food
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations

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