DoesLitomosoides sigmodontissynthesize dimethylethanolamine from choline?

Abstract

Juvenile female Litomosoides sigmodontis secrete a protein (Juv-p120) highly modified with dimethylethanolamine (DMAE). In an attempt to establish the source of this decoration worms were pulsed with [ 3 H]-choline and [ 3 H]-ethanolamine and the radio-isotope labelled products analysed. Both isotope labels were successfully taken up by the worms, as demonstrated by labelling of phospholipids with [ 3 H]-choline, being predominantly incorporated into phosphatidylcholine and [ 3 H]-ethanolamine into phosphatidylethanolamine. Isotope labelling of phosphatidylethanolamine was particularly striking with the worms taking up y30 times as much labelled ethanolamine as choline. It was possible to detect faint labelling of Juv-p120 with [ 3 H]-ethanolamine after prolonged exposure periods but, unlike the situation with the phospholipids, it was much more readily labelled with [ 3 H]-choline. When pulsing with [ 3 H]-ethanolamine it was also possible to detect isotope-labelled phosphatidylcholine, which may ultimately account for the low levels of labelling of Juv-p120. Overall our results raise the previously unconsidered but intriguing possibility that in L. sigmodontis, choline may be the precursor of DMAE.

Designing Anti-inflammatory Drugs from Parasitic Worms: A Synthetic Small Molecule Analogue of the Acanthocheilonema viteae Product ES-62 Prevents Development of Collagen-Induced Arthritis

“…11a is of course too small to be immunogenic, but it also possesses another feature that increases its candidature as a more effective version of ES-62 for therapeutic purposes. It contains a tertiary dimethylamino group in contrast to the quaternary trimethylammonium choline component of PC; previously we have shown that unlike choline, its dimethylamino analogue does not compete for binding to the myeloma protein TEPC 15, an antibody which recognizes PC . This suggests that 11a will not bind to endogenous anti-PC antibodies that are found in humans and which could conceivably interfere with activity of PC-containing SMAs.…”

“…It contains a tertiary dimethylamino group in contrast to the quaternary trimethylammonium choline component of PC; previously we have shown that unlike choline, its dimethylamino analogue does not compete for binding to the myeloma protein TEPC 15, an antibody which recognizes PC. 60 This suggests that 11a will not bind to endogenous anti-PC antibodies that are found in humans and which could conceivably interfere with activity of PC-containing SMAs. Furthermore, there is increasing evidence that natural anti-PC antibodies by an as yet unknown mechanism may in themselves be anti-inflammatory, protecting humans from diseases such as atherosclerosis, 61 and so this represents another reason for designing drugs that avoid interacting with them.…”

Helminth immunoregulation: The role of parasite secreted proteins in modulating host immunity

“…In the rodent filarial parasite Litomosoides sigmodontis , the major ES product is modified with DMAE (dimethylaminoethanol) [116], which contains one less methyl group than PC, giving rise to suggestions that DMAE may function immunologically in a manner similar to PC [117].…”