Activation of peritoneal macrophages by orally administered ether analogues of lysophospholipids.
Oral administration of dodecylglycerol, inflammatory product of cancerous tissues, and the alkyl lysophospholipid derivative, 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3-choline), greatly activated mouse peritoneal macrophages. The activation was dose related and was assessed as increased Fc-mediated ingestion of red blood cells, superoxide production, chemiluminescence activity, and incorporation of radioactive thymidine and leucine. Furthermore, the data show that dodecylglycerol or ET-18-OCH3-choline was capable of inducing equally high levels of macrophage activation and cytotoxic action on tumor cells, just as occurs with intraperitoneal administration. Dodecylglycerol appeared to activate the macrophages at a relatively lower dose (5 micrograms/mouse) than ET-18-OCH3-choline (15 micrograms/mouse). The optimal oral doses required to activate macrophages for ingestion and cytotoxic activities were relatively higher than previously observed when these agents were administered intraperitoneally. Thus, the dose difference provided crucial information for correlating oral dosages with in vivo concentration of these agents as bioassayed by macrophage activation. These observations have extended and further support our earlier findings that these agents are effective immunopotentiators and thus could therapeutically be used to activate macrophages for cytotoxic effects on tumor cells via the oral route.
Ngwenya
B Z
BZ
Department of Microbiology and Immunology, Hahnemann University School of Medicine, Philadelphia, Pennsylvania 19102-1192.
Fiavey
N P
NP
Mogashoa
M M
MM
D000284:Administration, Oral; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005134:Eye Neoplasms; D005989:Glycerides / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D007848:Laurates / Q000008:administration & dosage / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism; D008163:Luminescent Measurements; D008246:Lysophospholipids / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D050178:Monoglycerides; D010742:Phospholipid Ethers / Q000008:administration & dosage / Q000494:pharmacology*; D012175:Retinoblastoma; D013481:Superoxides / Q000378:metabolism
D005989:Glycerides; D007848:Laurates; D008246:Lysophospholipids; D050178:Monoglycerides; D010742:Phospholipid Ethers; D013481:Superoxides; C026659:edelfosine; C020777:monolaurin; D007930:Leucine