TY - JOUR
T1 - Inhibition of macrophage la expression by nitric oxide
AU - Sicher, Stanley C.
AU - Vazquez, Miguel A.
AU - Lu, Christopher Y.
PY - 1994/8/1
Y1 - 1994/8/1
N2 - Bacterial LPS inhibits the expression of la by macrophages stimulated by IFN-ã. We now present the following observations that suggest a causal relationship between nitric oxide (NO) and this inhibition of la expression: 1) NO production precedes inhibition of la, 2) the ability of LPS to inhibit la expression by IFN-γ stimulated macrophages is correlated in a dose-dependent fashion with NO production, 3) la expression is restored if NO production is inhibited by NG-monomethyl-L-arginine or culturing the macrophages in L-arginine-free medium, and 4) exogenous NO inhibits IFN-γ-stimulated la expression. Taken together these experiments indicate that NO inhibits macrophage expression of la. Furthermore, the following studies showed that inhibition of la by NO was not due to macrophage death: trypan blue exclusion, macrophage adhesion, conversion of the tetrazolium dye (MTT) to its formazan by a functioning electron transport system, and phagocytosis of IgG opsonized SRBCs. By inhibiting la expression, NO may inhibit Ag-presentation to T cells, secretion of IFN-γ by these T cells, and ultimately inhibit the IFNγ-dependent production of NO synthetase. This inhibitory mechanism may prevent excessive NO formation and tissue injury.
AB - Bacterial LPS inhibits the expression of la by macrophages stimulated by IFN-ã. We now present the following observations that suggest a causal relationship between nitric oxide (NO) and this inhibition of la expression: 1) NO production precedes inhibition of la, 2) the ability of LPS to inhibit la expression by IFN-γ stimulated macrophages is correlated in a dose-dependent fashion with NO production, 3) la expression is restored if NO production is inhibited by NG-monomethyl-L-arginine or culturing the macrophages in L-arginine-free medium, and 4) exogenous NO inhibits IFN-γ-stimulated la expression. Taken together these experiments indicate that NO inhibits macrophage expression of la. Furthermore, the following studies showed that inhibition of la by NO was not due to macrophage death: trypan blue exclusion, macrophage adhesion, conversion of the tetrazolium dye (MTT) to its formazan by a functioning electron transport system, and phagocytosis of IgG opsonized SRBCs. By inhibiting la expression, NO may inhibit Ag-presentation to T cells, secretion of IFN-γ by these T cells, and ultimately inhibit the IFNγ-dependent production of NO synthetase. This inhibitory mechanism may prevent excessive NO formation and tissue injury.
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M3 - Article
C2 - 8027556
AN - SCOPUS:0028243659
SN - 0022-1767
VL - 153
SP - 1293
EP - 1300
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -