Tumor necrosis factor release by murine macrophages stimulated by the cytotoxic ether lipid 1-O-hexadecyl-2-O-methyl-SN-glycero-3-phosphorylcholine (ET-18-O-OCH3).
The cytotoxic ether lipid 1-O-hexadecyl-2-O-methyl-SN-glycero-3-phosphorylcholine (ET-18-O-OCH3) is a structural analog of the mediator of inflammation platelet-activating factor (PAF). Recent studies demonstrated that ET-18-O-OCH3 activates human monocytes selectively at non-cytotoxic concentrations. The current studies determined the capacity of ET-18-O-OCH3 to stimulate release of TNF alpha by murine peritoneal macrophages. Macrophage receptors for ET-18-OCH3 and PAF were also assessed. ET-18-O-OCH3 and PAF stimulated TNF alpha release by resident BALB/c macrophages in the presence of LPS but not in the absence of this co-factor. In contrast, both ET-18-O_OCH3 and PAF stimulated TNF alpha release by thioglycollate-elicited macrophages in the absence of LPS although release was greater in the presence of this co-stimulus. Optimal stimulation of TNF alpha release occurred at 10(-14)-10(-11) M ET-18-O-OCH3 and PAF. Elicited macrophages and splenic macrophages from C57Bl/6 mice, unlike those from BALB/c mice, did not respond to 10(-15)-10(-8) M ET-18-O-OCH3 or PAF without or with LPS. Scatchard analysis of [3H]PAF binding to elicited BALB/c macrophages revealed the existence of high affinity receptors for PAF. In contrast, there was no evidence for receptors for ET-18-O-OCH3. ET-18-O-OCH3 did not compete with PAF for binding; macrophage activation by ET-18-O-OCH3 was not stereospecific; and, binding studies using [3H]ET-18-O-OCH3 did not reveal saturable binding characteristic of binding to specific receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Shames
R
R
Department of Medicine, Dartmouth Medical School, Lebanon, NH 03756.
Ruis
N M
NM
Valone
F H
FH
D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013237:Stereoisomerism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; C053411:1-O-hexadecyl-2-C-methyl-3-phosphatidylcholine