| 8045673 |
Shames R, Ruis NM, Valone FH: 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). Int J Immunopharmacol. 1994 Apr;16(4):335-43.
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) |
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