PMID- 7634340
OWN - NLM
STAT- MEDLINE
DCOM- 19950911
LR  - 20131121
IS  - 0008-8749 (Print)
IS  - 0008-8749 (Linking)
VI  - 164
IP  - 1
DP  - 1995 Aug
TI  - The induction and augmentation of macrophage tumoricidal responses by 
      platelet-activating factor.
PG  - 105-12
AB  - Platelet-activating factor (PAF) has previously been shown to stimulate 
      intracellular signal transductional events similar to the macrophage tumoricidal 
      activators interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). Macrophages 
      stimulated with IFN-gamma 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-alpha (TNF alpha)-mediated cytolysis by macrophages. Therefore, 
      the purpose of this study was to determine whether PAF, in comparison with 
      IFN-gamma and LPS, could stimulate macrophages for both TNF alpha- and non-TNF 
      alpha-mediated tumoricidal activity. For this, the activation of macrophages for 
      a cytolytic response was characterized by the production of TNF alpha and nitric 
      oxide (NO2-), as well as, their ability to kill select tumor cells. PAF together 
      with IFN-gamma stimulated macrophage secretion of NO2-. In addition, PAF enhanced 
      IFN-gamma- and LPS-stimulated NO2- production. PAF, together with IFN-gamma, also 
      activated macrophages for tumoricidal activity against TNF alpha-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-gamma. Moreover, PAF enhanced macrophage tumoricidal activity when added with 
      LPS and IFN-gamma. With respect to TNF alpha production, macrophages activated 
      with high concentrations of PAF stimulated significant levels of TNF alpha 
      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 TNF alpha-sensitive tumor cell. In addition, PAF 
      significantly enhanced LPS-induced TNF alpha production. Thus, PAF can play a 
      modulatory role in the activation for non-TNF alpha-mediated tumoricidal activity 
      of macrophages.
FAU - Howard, A D
AU  - Howard AD
AD  - Department of Cell Biology and Human Anatomy, School of Medicine, University of 
      California, Davis 95616-8643, USA.
FAU - Erickson, K L
AU  - Erickson KL
LA  - eng
GR  - CA 47050/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Cell Immunol
JT  - Cellular immunology
JID - 1246405
RN  - 0 (Platelet Activating Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Animals
MH  - Cytotoxicity, Immunologic/drug effects
MH  - Dose-Response Relationship, Immunologic
MH  - Female
MH  - Macrophage Activation/*drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neoplasms, Experimental/immunology
MH  - Nitric Oxide/biosynthesis
MH  - Platelet Activating Factor/*pharmacology
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/analysis/drug effects/metabolism
EDAT- 1995/08/01 00:00
MHDA- 1995/08/01 00:01
CRDT- 1995/08/01 00:00
PHST- 1995/08/01 00:00 [pubmed]
PHST- 1995/08/01 00:01 [medline]
PHST- 1995/08/01 00:00 [entrez]
AID - S0008-8749(85)71148-3 [pii]
AID - 10.1006/cimm.1995.1148 [doi]
PST - ppublish
SO  - Cell Immunol. 1995 Aug;164(1):105-12. doi: 10.1006/cimm.1995.1148.