Macrophage Migration Inhibition Induced by MDP, LPS, PMA, and MIF/MAF: Reversal by Macrophage Migration Enhancement Factor (MEF), L-Fucose, L-Fucosyl BSA, D-Mannose, and D-Mannosyl BSA

Abstract

Our data establish that migration inhibition factor (MIF) and migration enhancement factor (MEF) mutually neutralize the effect of each other in a concentration-dependent manner. The monosaccharides L-fucose and D-mannose were also shown to reverse MIF and additionally to stimulate alveolar macrophage (AM) migration in the absence of MIF. The specific activity of these sugars was increased 200-fold when conjugated to bovine serum albumin (BSA). Macrophage activation is usually observed concurrently with migration inhibition when macrophages are incubated with MIF preparations. Migration inhibition occurred also when AM were incubated in the presence of known metabolic activators (MDP, PMA, and LPS). It was found that L-fucose, D-mannose, L-fucosyl BSA, and D-mannosyl BSA could reverse migration inhibition caused by MIF as well as by these metabolic activators. These observations suggest that reversal of MIF by L-fucose is unexplained solely on the basis that L-fucose is functioning as a competitive inhibitor; instead, they suggest that MEF and the above sugars and their conjugates stimulate AM through a receptor system different from the MIF receptor. These observations support the concept that MEF is an important macrophage modulator in CMI responses.

Production of Macrophage Migration Inhibitory Factor by Human and Murine Neuroblastoma

“…This activity was inhibited both by anti-MIF antibody and by 10 mM L-fucose. L-Fucose has been reported to reverse MIF activity, presumably by interfering with the MIF receptor system [21]. Culture supernatants from both VNB-B and SK-N-SH cell lines exhibited similar activity (not shown).…”

“…4). This activity was inhibited by L-fucose, a monosaccharide reported to inhibit MIF binding to its receptor [21]. Inhibition with anti-MIF antibody was not found to be significant in our assays.…”

The microglial activation state regulates migration and roles of matrix-dissolving enzymes for invasion

“…Previous reports are inconsistent, and while the reasons are not clear, the effect of LPS on migration might depend on species and strain, cell type and age. Impaired migration has been reported for neonatal rat [31] and adult human microglia [32], and for guinea pig peritoneal macrophages [33] and rabbit alveolar macrophages [34]. Conversely, some studies reported that LPS can increase migration in the RAW264.7 macrophage cell line [35,36] and primary rat peritoneal macrophages, but the LPS dose was not stated [35].…”

The Novel Anti-Rheumatic Drug TA-383 Has a Macrophage Migration Enhancing Activity.

“…The mixture of MIF and MEF resulted in the mutual neutralization of each activity (7,8). The monosaccharides L-fucose, D-mannose, L-galactose, and their BSA conjugates were also shown to neutralize MIF activity and have potential to stimulate alveolar macro phage (AM) migration by themselves (8,9). We speculat ed that compounds with MEF activity might induce the dispersion of infiltrated macrophages from the inflamma tory sites and thereby exhibit anti-inflammatory activity.…”

“…TA-383 might be able to inhibit MIF activity through the induction of MEF because MEF can block the activity of MIF (8,9), However, the possible role of MEF in a cell-mediated im mune response is unclear. MIF activity was reported to be associated with DTH (1, 2), the enhancement of macro phage adherence and phagocytosis, and up-regulation of genes encoding human leucocyte antigen (HLA)-DR and IL-1 (5).…”