The ablation of the protein kinase Raf-1 renders cells hypersensitive to apoptosis despite normal regulation of extracellular signal–regulated kinases, which suggests that apoptosis protection is mediated by a distinct pathway. We used proteomic analysis of Raf-1 signaling complexes to show that Raf-1 counteracts apoptosis by suppressing the activation of mammalian sterile 20–like kinase (MST2). Raf-1 prevents dimerization and phosphorylation of the activation loop of MST2 independently of its protein kinase activity. Depletion of MST2 from Raf-1 ^–/– mouse or human cells abrogated sensitivity to apoptosis, whereas overexpression of MST2 induced apoptosis. Conversely, depletion of Raf-1 from Raf-1 ^+/+ mouse or human cells led to MST2 activation and apoptosis. The concomitant depletion of both Raf-1 and MST2 prevented apoptosis.

Three major phagocytic populations in the mouse were tested in vitro for killing of Candida albicans by means of ⁵¹Cr release assay: early inflammatory peritoneal polymorphonuclear cells (PMN), unfractionated or adherent spleen cells and resident peritoneal macrophages (PEC). Considerable candidacidal activity was found in the early inflammatory neutrophil and adherent spleen cell populations. On the contrary, only limited activity was found to be associated with resident peritoneal macrophages. The phagocytic killing apparently involved multiple mechanisms. Les trois principales populations de phagocytes de Souris ont été essayées in vitro pour la lyse de Candida albicans au moyen de la méthode de libération du ⁵¹Cr: ce sont les polynucléaires péritonéaux de l'inflammation précoce (PMN), les cellules spléniques entières ou adhérentes et les cellules résidentes de l'exsudat péritonéal (PEC). Une activité candidicide importante se trouve associée aux populations de neutrophiles de l'inflammation précoce et aux cellules spléniques adhérentes. Au contraire, les macrophages péritonéaux résidents ne montrent qu'une activité limitée. La destruction phagocytaire semble ainsi dépendre de mécanismes multiples.