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Superoxide production by macrophages stimulatedin vivo with synthetic ether lipids

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Lipids

Abstract

The anticancer activity of synthetic ether lipids may depend in part upon their ability to activate cells of the monocyte/macrophage lineage. In the present study, we have sought to determine whether 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OMe) and related ether lipids enhance superoxide production by mouse peritoneal macrophages. Ether lipids were administered intraperitoneally to C57BL/6 mice 4 d after injection with thioglycollate broth. Elicited peritoneal macrophages were harvested and purified one day later, and superoxide production was detected by measuring the superoxide dismutase inhibitable reduction of cytochrome c. Low levels of superoxide were secreted by macrophages in the absence of phorbol 12-myristate 13-acetate (PMA). When PMA was addedin vitro to macrophages from ET-18-OMe-treated mice, these cells secreted 194.2 nmol superoxide/mg protein in comparison to 53.5 nmol superoxide/mg protein for PMA-treated control cells. Thein vitro treatment of the macrophages with ET-18-OMe was not effective in stimulating superoxide secretion. Macrophages harvested from mice treated with a series of ether lipids (with and without phosphorus) were examined, and superoxide secretion was found to vary with structure. AM-18-OEt and CP-7 were the most effective compounds, secreting 8.6 and 11.9 times more superoxide, respectively, than PMA-stimulated control cells. Moreover, direct cytotoxicity of the compounds for HL60 human promyelocytic leukemic cells did not necessarily correlate with the ability of each drug to increase macrophage superoxide production.

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Abbreviations

ALP:

alkyllysophospholipids

AM-18-OEt:

1-N-heptadecylamido-2-O-ethyl-rac-glycero-3-phosphocholine

ET-16SOEt:

1-S-hexadecyl-2-O-ethyl-rac-glycero-3-phosphocholine

ET-18-OMe:

1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine

CP-7:

rac-1-S-hexadecyl-2-O-methylthiopropyl-3-N,N-dimethyl-β-hydroxyethyl ammonium bromide

CP-14:

rac-1-O-hexadecyl-2-methylglycerol

CP-37:

rac-1-O-β-naphthyl-2-O-methylpropyl-3-N,N-dimethyl-β-hydroxyethyl ammonium bromide

HBSS:

Hank's balanced salt solution

ID50 :

the amount of compound required to reduce [3H]thymidine incorporation into DNA to 50% of the control value

LPC:

lysophosphatidylcholine

MEM:

Eagle's minimal essential medium

O2 − :

superoxide

PBS:

phosphate buffered saline

PC:

phosphatidylcholine

PMA:

phorbol 12-myristate 13-acetate

SOD:

superoxide dismutase

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Authors and Affiliations

  1. Department of Biochemistry, Boston University School of Medicine, 80 E. Concord St., 02118, Boston, MA

    Barbara M. Schreiber, Matthew D. Layne & Edward J. Modest

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  1. Barbara M. Schreiber
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  2. Matthew D. Layne
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Schreiber, B.M., Layne, M.D. & Modest, E.J. Superoxide production by macrophages stimulatedin vivo with synthetic ether lipids. Lipids 29, 237–242 (1994). https://doi.org/10.1007/BF02536327

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