SummaryExpression of the macrophage mannose receptor is inhibited by interferon y (IFN-30, a T helper type 1 (Th-1)-derived lymphokine. Interleukin 4 (I1:4), a Th-2 lymphocyte product, upregulates major histocompatibility class II antigen expression but inhibits inflammatory cytokine production by macrophages. We have studied the effect of Ib4 on expression of the macrophage mannose receptor (MMR) by elicited peritoneal macrophages. We found that recombinant murine Ib4 enhances MMR surface expression (10-fold) and activity (15-fold), as measured by the respective binding and degradation of 12SI-mannose-bovine serum albumin. Polymerase chain reaction analysis of cDNAs from purified primary macrophage populations revealed that MMR, but not lysozyme or tumor necrosis factor ~ mRNA levels were markedly increased by IL-4. The above effects were associated with morphologic changes. These data establish II-4 as a potent and sdective enhancer of murine MMR activity in vitro. IL-4 induces inflammatory macrophages to adopt an alternative activation phenotype, distinct from that induced by IFN-% characterized by a high capacity for endocytic clearance of mannosylated ligands, enhanced (albeit restricted) MHC class II antigen expression, and reduced proinflammatory cytokine secretion. The macrophage mannose receptor (MMR) (previously called the mannosyl fucosyl receptor [MFR]) is an important phagocytic receptor mediating the binding and ingestion of micro-organisms with surface mannose residues and soluble mannose-containing glycoproteins. It is expressed on resident and elicited peritoneal macrophages and alveolar macrophages, not expressed on monocytes, and at low levels on Bacill~-Calmette-Guerin (BCG)-or IFN-3~-activated macrophages (1). Therefore, the MMR is a marker of the resident and elicited, but not IFN-y-activated, macrophage phenotype. MMR activity is increased by steroids and IFN-ol and -fl, and is inversely correlated with MHC class II antigen expression, which is induced on immunologically stimulated macrophages and used as a marker of activation. ID4, predominantly produced by activated Th cells of the type 2 phenotype and non-B, non-T, FcER + cells, has pleiotropic effects on a variety of immune and nonimmune cells. As it induces the expression of MHC class II antigen on B cells and monocytes, and enhances macrophage tumoricidal activity, it has been described as a macrophage-activating factor (2). However, the tumoricidal activity is confined to selected target cell lines, and only HLA-DR and HLA-DP but not HLA-DQ MHC class II molecules are induced by ID4. In addition, IL-4 induces MHC class II antigen expression on restricted macrophage populations. In contrast, IFN-3' induces all three class II molecules on most if not all macrophages (3, 4). Furthermore, Ib4 inhibits the expression of pro-inflammatory cytokine genes such as I1:1, TNF, and I1:8, and synergizes with steroids to inhibit macrophage proinflammatory activity (5-9). In addition, I1:4 inhibits superoxide anion release from PMA or zymosan-treat...

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Budding yeast can be considered to have two distinct lifespans: (a) a replicative (budding, non-chronological) lifespan, measured as the number of daughters produced by each actively dividing mother cell; and (ii) a chronological lifespan, measured as the ability of stationary cultures to maintain viability over time. In non-dividing cells, essential components that become damaged cannot be diluted out through cell division but must, of necessity, be turned over and renewed. By elevating stress resistances, many of the activities needed for such renewal should be elevated with commensurate reduction in the steady-state levels of damaged cell components. Therefore, chronological lifespan in particular might be expected to relate to stress resistance. For yeast to attain a full chronological lifespan requires the expression of the general stress response. It is more important, though, that the cells should be efficiently adapted to respiratory maintenance, since it is cultures grown to stationary phase on respiratory media that usually display the longest chronological lifespans. For this reason, respiration-adapted cells potentially provide a better model of chronological ageing than cultures pre-grown on glucose.