Molecular mechanisms of toxicant-induced immunosuppression: role of second messengers.
Changes in immunocompetence following chemical exposure have been established for a wide variety of unrelated agents. For the vast majority of immunotoxic compounds thus far identified, disruption of normal immune function is clearly mediated through direct interactions between the agent, or its metabolite, and immunocompetent cells. Regardless of whether this interaction occurs at the level of the cell membrane or at intracellular sites, basic regulatory processes mediated by second messengers are often altered. These alterations can ultimately result in immunologic dysfunction, which is most often manifested as immunosuppression. The specific disruptions in intracellular signaling produced by a number of immunotoxic compounds have now been identified, leading to a basic understanding of their molecular mechanism of action. Equally important, through the application of these agents as biological probes, new insights have been gained pertaining to which intracellular processes control which cellular functions within various populations of immunocompetent cells.
Holsapple
M P
MP
Toxicology Research Laboratory, Dow Chemical Company, Midland, Michigan 48674, USA.
Karras
J G
JG
Ledbetter
J A
JA
Schieven
G L
GL
Burchiel
S W
SW
Davila
D R
DR
Schatz
A R
AR
Kaminski
N E
NE
D000067956:Adenylyl Cyclase Inhibitors; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002186:Cannabinoids / Q000633:toxicity; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D000922:Immunotoxins / Q000633:toxicity*; D018384:Oxidative Stress; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000067956:Adenylyl Cyclase Inhibitors; D002186:Cannabinoids; D000922:Immunotoxins; D000072317:Polychlorinated Dibenzodioxins; D011084:Polycyclic Aromatic Hydrocarbons; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins; D002118:Calcium