Mechanism of Action of Migration Inhibitory Factor (Mif)

Abstract

The initial interaction between migration inhibitory factor (MIF) and the guinea pig alveolar and peritoneal macrophage was studied. MIF-containing supernatants were generated from sensitized lymph node lymphocytes obtained from guinea pigs immunized with bovine gamma globulin in complete Freund's adjuvant. MIF-containing supernatants were markedly inhibitory for the migration of the peritoneal macrophage but had no effect on the alveolar macrophage. A linear relationship was observed between per cent inhibition of migration and serial twofold dilution of supernatant. Reexpressed in arbitrary MIF units, this relationship reflects a dose-response relationship with saturation characteristics. Pulse exposure of peritoneal macrophages to MIF resulted in adsorption of MIF onto both viable and nonviable cells with corresponding depletion of supernatant MIF. The alveolar macrophage did not adsorb MIF. Pulse adsorption of MIF onto the peritoneal macrophage is dependent on time, temperature, and cell number. Pretreatment of the cells with proteolytic enzyme prevents the adsorption of MIF while leaving migration unaffected. These observations support the existence of a specific cell surface receptor for MIF. The existence of such a receptor provides selectivity of immune modulation of macrophage populations by lymphocytes in delayed hypersensitivity reactions.

Development of Cellular and Humoral Immunity in the Respiratory Tract of Rabbits to Pseudomonas Lipopolysaccharide

“…Alveolar macrophages were capable of responding to MIF in this rabbit system, contrary to reported findings in guinea pigs (38). Although lymphocytes accounted for only 7% of respiratory cells, it has been shown (31) that as few as 1% sensitized lymphocytes are sufficient to inhibit the migration of a population of normal unsensitized macrophages.…”

Partial Purification of Guinea Pig MIF by Affinity Column Chromatography Using Macrophages

“…The eluted fractions did not show any MIF activity, although in some cases the macrophage migration was reduced slightly (data not shown). DISCUSSION Leu et al reported that MIF could be removed from supernatants by incubation with macrophages (11). Other evidence of the presence of macrophage receptors for MIF was suggested by David et al, who showed that trypsinized macrophages failed to respond to MIF but regained their ability to do so after a 24 hr culture in vitro (7).…”

“…Prior to development of the affinity column chromatography using macrophages, an investigation was performed to determine whether MIF can be adsorbed on live macrophages as reported by Leu et al (11). As shown in Table 1 (supernatants A & B), approx.…”

“…In guinea pig MIF, Leu et al (11) have reported that MIF was adsorbed by macrophages when they were incubated together. Remold (14) has described the suppression of MIF by (L)-fucose, suggesting that this sugar may be an integral part of macrophages interacting with MIF.…”

“…Recently, it has become evident that macrophages or neutrophils may have receptors for several lymphokines and the receptors consist of sugar moieties in the cell surface membrane (1,8,11,14,16,19). In guinea pig MIF, Leu et al (11) have reported that MIF was adsorbed by macrophages when they were incubated together.…”