Immune modification due to chemical interference with transmembrane signalling: application to polycyclic aromatic hydrocarbons.
Triggering of the T-cell antigen receptor complex and some other surface molecules is coupled to the phosphodiesterase (phospholipase C)-mediated hydrolysis of membrane phosphoinositides, in particular, phosphatidylinositol-4,5-biphosphate (PiP2). PiP2 hydrolysis generates two products, inositol 1,4,5-triphosphate and diacylglycerol, which act in concert as second messengers to increase the free intracellular calcium concentration and activate protein kinase C, respectively, thereby stimulating subsequent events leading to cellular activation and proliferation. Transmembrane signalling in T-lymphocytes represents a potential target for designated drugs as well as immunotoxicants. Immunotoxic effects of polycyclic aromatic hydrocarbons are discussed in the view of interaction with transmembrane signalling in the T-lymphocyte.
Pallardy
M
M
Laboratoire de Toxicologie, Faculté de Pharmacie Paris XI, Chatenay-Malabry, France.
Mishal
Z
Z
Lebrec
H
H
Bohuon
C
C
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D010716:Phosphatidylinositols / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015290:Second Messenger Systems; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D004075:Diglycerides; D010716:Phosphatidylinositols; D011948:Receptors, Antigen, T-Cell; D015127:9,10-Dimethyl-1,2-benzanthracene; D002118:Calcium