A dialysable acid factor from human leukocyte extracts activates tumor cell lysis mediated by human monocytes and natural killer cells

Dialysable human leukocyte extract contains an acid natural killer (NK) cytotoxicity-stimulating factor, CySF-L1, which can be enriched by ion exchange chromatography. NK-cytotoxicity of human peripheral blood mononuclear cells (PBMC) against human K562 and HT29 tumor cells was strongly enhanced after 72 h pre-incubation with the factor. The CySF-L1-specific stimulation of PBMC required the presence of monocytes. The cytotoxic effector cells activated during preincubation of PBMC with CySF-1 were identified as monocytes and as NK cells present in the fraction of large granular lymphocytes (LGL). Selective cell depletion studies with LGL containing subpopulations (free of monocytes) indicated that the activated NK cells express CD 16 (Leu 11) and CD8 (T8) markers and the majority of them also the Leu7 marker. Analysis of the changes of surface marker expression of human PBMC during preincubation with CySF-L1 revealed an efficient stimulation of CD8 and TfR (transferrin receptor) expression, partly in conjunction with diminished expression of CD4 (T4). In vivo application of CySF-L1 after tumor challenge induced reduction of the incidence of tumor take and tumor development in mice

Characterization of the zinc metalloprotease of Streptococcus suis serotype 2

Abstract Streptococcus suis is a swine pathogen and zoonotic agent responsible for meningitis and septic shock. Although several putative virulence factors have been described, the initial steps of the S. suis pathogenesis remain poorly understood. While controversial results have been reported for a S. suis serotype 2 zinc metalloprotease (Zmp) regarding its IgA protease activity, recent phylogenetic analyses suggested that this protein is homologous to the ZmpC of Streptococcus pneumoniae, which is not an IgA protease. Based on the previously described functions of metalloproteases (including IgA protease and ZmpC), different experiments were carried out to study the activities of that of S. suis serotype 2. First, results showed that S. suis, as well as the recombinant Zmp, were unable to cleave human IgA1, confirming lack of IgA protease activity. Similarly, S. suis was unable to cleave P-selectin glycoprotein ligand-1 and to activate matrix metalloprotease 9, at least under the conditions tested. However, S. suis was able to partially cleave mucin 16 and syndecan-1 ectodomains. Experiments carried out with an isogenic Δzmp mutant showed that the Zmp protein was partially involved in such activities. The absence of a functional Zmp protein did not affect the ability of S. suis to adhere to porcine bronchial epithelial cells in vitro, or to colonize the upper respiratory tract of pigs in vivo. Taken together, our results show that S. suis serotype 2 Zmp is not a critical virulence factor and highlight the importance of independently confirming results on S. suis virulence by different teams