Abstract
Platelet-activating factor (PAF) has previously been shown to stimulate intracellular signal transductional events similar to the macrophage tumoricidal activators interferon-γ (IFN-γ) and lipopolysaccharide (LPS). Macrophages stimulated with IFN-γ and LPS utilize various cytolytic mediators in order to kill tumor cells. However, PAF has been shown to only induce and enhance tumor necrosis factor-α (TNFα)-mediated cytolysis by macrophages. Therefore, the purpose of this study was to determine whether PAF, in comparison with IFN-γ and LPS, could stimulate macrophages for both TNFγ- and non-TNFγ-mediated tumoricidal activity. For this, the activation of macrophages for a cytolytic response was characterized by the production of TNFγ and nitric oxide (NO- 2), as well as, their ability to kill select tumor cells. PAF together with IFN-γ stimulated macrophage secretion of NO- 2. In addition, PAF enhanced IFN-γ- and LPS-stimulated NO- 2 production. PAF, together with IFN-γ, also activated macrophages for tumoricidal activity against TNFγ-resistant tumor cells. In assays to determine the temporal sequence of activation, increased tumor cell cytolysis was observed only when macrophages were first treated with IFN-γ. Moreover, PAF enhanced macrophage tumoricidal activity when added with LPS and IFN-γ. With respect to TNFγ production, macrophages activated with high concentrations of PAF stimulated significant levels of TNFγ compared to macrophages without PAF. A similar level was observed following multiple additions of a lower concentration of PAF, Also, PAF induced macrophage cytolytic activity against a TNFγ-sensitive tumor cell. In addition, PAF significantly enhanced LPS-induced TNFα production. Thus, PAF can play a modulatory role in the activation for non-TNFγ-mediated tumoricidal activity of macrophages.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 105-112 |
| Number of pages | 8 |
| Journal | Cellular Immunology |
| Volume | 164 |
| Issue number | 1 |
| DOIs | |
| State | Published - Aug 1995 |
Fingerprint
ASJC Scopus subject areas
- Immunology
- Cell Biology
Cite this
The Induction and Augmentation of Macrophage Tumoricidal Responses by Platelet-Activating Factor. / Howard, Angela D.; Erickson, Kent L.
In: Cellular Immunology, Vol. 164, No. 1, 08.1995, p. 105-112.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The Induction and Augmentation of Macrophage Tumoricidal Responses by Platelet-Activating Factor
AU - Howard, Angela D.
AU - Erickson, Kent L
PY - 1995/8
Y1 - 1995/8
N2 - Platelet-activating factor (PAF) has previously been shown to stimulate intracellular signal transductional events similar to the macrophage tumoricidal activators interferon-γ (IFN-γ) and lipopolysaccharide (LPS). Macrophages stimulated with IFN-γ and LPS utilize various cytolytic mediators in order to kill tumor cells. However, PAF has been shown to only induce and enhance tumor necrosis factor-α (TNFα)-mediated cytolysis by macrophages. Therefore, the purpose of this study was to determine whether PAF, in comparison with IFN-γ and LPS, could stimulate macrophages for both TNFγ- and non-TNFγ-mediated tumoricidal activity. For this, the activation of macrophages for a cytolytic response was characterized by the production of TNFγ and nitric oxide (NO- 2), as well as, their ability to kill select tumor cells. PAF together with IFN-γ stimulated macrophage secretion of NO- 2. In addition, PAF enhanced IFN-γ- and LPS-stimulated NO- 2 production. PAF, together with IFN-γ, also activated macrophages for tumoricidal activity against TNFγ-resistant tumor cells. In assays to determine the temporal sequence of activation, increased tumor cell cytolysis was observed only when macrophages were first treated with IFN-γ. Moreover, PAF enhanced macrophage tumoricidal activity when added with LPS and IFN-γ. With respect to TNFγ production, macrophages activated with high concentrations of PAF stimulated significant levels of TNFγ compared to macrophages without PAF. A similar level was observed following multiple additions of a lower concentration of PAF, Also, PAF induced macrophage cytolytic activity against a TNFγ-sensitive tumor cell. In addition, PAF significantly enhanced LPS-induced TNFα production. Thus, PAF can play a modulatory role in the activation for non-TNFγ-mediated tumoricidal activity of macrophages.
AB - Platelet-activating factor (PAF) has previously been shown to stimulate intracellular signal transductional events similar to the macrophage tumoricidal activators interferon-γ (IFN-γ) and lipopolysaccharide (LPS). Macrophages stimulated with IFN-γ and LPS utilize various cytolytic mediators in order to kill tumor cells. However, PAF has been shown to only induce and enhance tumor necrosis factor-α (TNFα)-mediated cytolysis by macrophages. Therefore, the purpose of this study was to determine whether PAF, in comparison with IFN-γ and LPS, could stimulate macrophages for both TNFγ- and non-TNFγ-mediated tumoricidal activity. For this, the activation of macrophages for a cytolytic response was characterized by the production of TNFγ and nitric oxide (NO- 2), as well as, their ability to kill select tumor cells. PAF together with IFN-γ stimulated macrophage secretion of NO- 2. In addition, PAF enhanced IFN-γ- and LPS-stimulated NO- 2 production. PAF, together with IFN-γ, also activated macrophages for tumoricidal activity against TNFγ-resistant tumor cells. In assays to determine the temporal sequence of activation, increased tumor cell cytolysis was observed only when macrophages were first treated with IFN-γ. Moreover, PAF enhanced macrophage tumoricidal activity when added with LPS and IFN-γ. With respect to TNFγ production, macrophages activated with high concentrations of PAF stimulated significant levels of TNFγ compared to macrophages without PAF. A similar level was observed following multiple additions of a lower concentration of PAF, Also, PAF induced macrophage cytolytic activity against a TNFγ-sensitive tumor cell. In addition, PAF significantly enhanced LPS-induced TNFα production. Thus, PAF can play a modulatory role in the activation for non-TNFγ-mediated tumoricidal activity of macrophages.
UR - http://www.scopus.com/inward/record.url?scp=0029102977&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029102977&partnerID=8YFLogxK
U2 - 10.1006/cimm.1995.1148
DO - 10.1006/cimm.1995.1148
M3 - Article
C2 - 7634340
AN - SCOPUS:0029102977
VL - 164
SP - 105
EP - 112
JO - Cellular Immunology
JF - Cellular Immunology
SN - 0008-8749
IS - 1
ER -