Intracellular and extracellular NO differentially modulates the stress response and apoptosis in macrophages exposed to the influence of biological or physical factors.
We studied the role of extracellular and intracellular NO in the regulation of the stress response and apoptosis in macrophages of proinflammatory and antiinflammatory phenotypes under the influence of S. aureus and heat shock. Blockade of extracellular nitric oxide synthesis in cells with antiinflammatory phenotype inhibited the stress response induced by S. aureus and heat shock. The decrease in extracellular nitric oxide concentration around antiinflammatory macrophages potentiated the stress response induced by S. aureus, but had no effect on the stress response induced by heat shock. Hence, intracellular NO mediates the stress response induced by S. aureus and heat shock, while extracellular NO inhibits the stress response induced by S. aureus, but has no effect on the stress response induced by heat shock. In cells with antiinflammatory phenotype, intracellular NO plays an antiapoptotic role. S. aureus and heat shock did not cause apoptosis in macrophages with proinflammatory phenotype, while intracellular NO did not play a role in antiapoptotic activity of the proinflammatory phenotype. Extracellular NO synthesized by macrophages protects these cells from apoptosis induced by S. aureus and heat shock.
Malysheva
E V
EV
Moscow State Medical Stomatological University.
Kruglov
S V
SV
Nazarov
V A
VA
Manukhina
E B
EB
Malyshev
I Yu
IY
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D053938:DNA Fragmentation; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D007249:Inflammation / Q000139:chemically induced; D008070:Lipopolysaccharides; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology*; D013211:Staphylococcus aureus / Q000276:immunology; D000338:beta-Aminoethyl Isothiourea / Q000494:pharmacology
D018840:HSP70 Heat-Shock Proteins; D008070:Lipopolysaccharides; D000338:beta-Aminoethyl Isothiourea; D009569:Nitric Oxide