Induction of macrophage antitumor activity by acetylated low density lipoprotein containing lipophilic muramyl tripeptide

J. M. Shaw, W. S. Futch, L. B. Schook

Research output: Contribution to journalArticle

Abstract

A method has been developed for the selective delivery of lipophilic immunomodulators to macrophages, which results in the induction of antitumor activity. This method utilizes exhaustively acetylated low density lipoprotein (acetyl-LDL) to deliver the lipophilic immunomodulator, muramyl tripeptide phosphatidylethanolamine (MTP-PtdEtn; amide composed on N-acetylmuramyl-L-alanyl-D-isoglutamyl-L-alanine and dipalmitoyl phosphatidylethanolamine) to macrophages (M∅) by means of a scavenger lipoprotein receptor pathway. The binding of acetyl-LDL:MTP-PtdEtn to M∅ showed specificity since minimal competition was observed in the presence of excess native LDL or phosphatidylcholine/cholesterol liposomes. Additional binding studies showed that acetyl-LDL may serve as a suitable delivery vehicle to a wide variety of M∅ in different stages of activation. Cytostatic and tumoricidal activities by thioglycolate-elicited M∅ against two tumor cell lines were examined in vitro following incubation with the acetyl-LDL:MTP-PtdEtn complex. Cytostatic activity against B16F10 melanoma cells was induced after the incubation of thioglycolate-elicited M∅ with a minimum of 25 μg of acetyl-LDL protein containing 2.5 μg of bound MTP-PtdEtn (~40 molecules per particle of acetyl-LDL). The induction of cytostasis was not affected by liposome bilayers, which were also endocytosed by the M∅. In addition, tumoricidal activity against P815 mastocytoma cells was demonstrated at a 40:1 effector-to-target ratio using 18 μg of the acetyl-LDL:MTP-PtdEtn complex containing 3.6 μg of MTP-PtdEtn (~80 molecules per particle). These studies describe a method for the induction of antitumor activity by use of a chemically modified serum component, acetyl-LDL, to direct lipophilic immunomodulators to M∅.

Original languageEnglish (US)
Pages (from-to)6112-6116
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume85
Issue number16
DOIs
StatePublished - 1988

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Induction of macrophage antitumor activity by acetylated low density lipoprotein containing lipophilic muramyl tripeptide'. Together they form a unique fingerprint.

  • Cite this