Glycolipid-dependent interaction between human migration-inhibitory factor and mononuclear phagocytes.
It has been previously established in the guinea pig that the response of peritoneal macrophages to migration inhibitory factor (MIF) is enhanced by a macrophage glycolipid and that gangliosides reversibly bind MIF. This suggests that glycolipids function as cell surface receptors for MIF. In this report, it is demonstrated that the response of human peripheral blood monocytes to human MIF is augmented by preincubation of these cells with glycolipid-enriched material extracted from the human macrophage-like cell line U937 or human peripheral blood monocytes and with a purified glycolipid from guinea pig peritoneal macrophages. In addition, a mixed ganglioside preparation from bovine brain shows the same effect. In contrast, the pure gangliosides, GM1 and GD1a, and glycolipids from the HL-60 cell line, which is a MIF-unresponsive cell line, were not able to enhance the response to human MIF. The specificity of enhancement by particular glycolipids could not be attributed to an increased uptake of only enhancing glycolipids since there was no significant difference between the association of monocytes with radioactive liposomes containing biologically active or inactive glycolipids. Pronase treatment did not affect the enhancing activity of the U937 glycolipid-enriched material. Incubation of cells with glycolipids results in enhancement only if done at 37 degrees C and not at 4 degrees C. Therefore, the association of lipid with the monocyte surface appears to be dependent on temperature. Further evidence for the receptor nature of these enhancing glycolipids is provided by experiments involving affinity purification experiments. Coupling of bovine brain mixed gangliosides to agarose resulted in a matrix capable of reversibly binding MIF. GD1a-agarose was inactive in this respect.
D000818:Animals; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000378:metabolism; D006017:Glycolipids / Q000494:pharmacology*; D006168:Guinea Pigs; D006801:Humans; D008081:Liposomes; D016403:Lymphoma, Large B-Cell, Diffuse; D008263:Macrophage Migration-Inhibitory Factors / Q000302:isolation & purification / Q000502:physiology*; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D013696:Temperature
D006017:Glycolipids; D008081:Liposomes; D008263:Macrophage Migration-Inhibitory Factors; D005677:G(M1) Ganglioside; D002784:Cholesterol