Eotaxin but not MCP-3 induces eosinophil influx into nasal fluid in allergic patients.

BACKGROUND: Eotaxin and MCP-3 (CC chemokines), owing to their preferential action on eosinophils, seem to be the very importance in the patophysiology of allergic rhinitis and asthma. The purpose of this study was to examine the effect of intranasally administered eotaxin and MCP-3 after specific allergen priming on the influx of inflammatory cells and their soluble mediators into the nasal mucosa. METHODS: Eotaxin and MCP-3 have been applied intranasally at the increasing doses of 1, 5 and 10 microg to allergic patients after allergen priming. The 'nasal pool' technique was used. The cell count and biochemical parameters in nasal lavage were evaluated before 30 min, and 4 and 24 h after the challenge with chemokines. RESULTS: Both eotaxin and MCP-3 induced the increase in clinical 'score' lasting till 24 h. Eosinophil influx into nasal mucosa after provocation with eotaxin was also observed. The challenge with MCP-3 did not induce any significant changes in nasal lavage fluid. CONCLUSIONS: Eotaxin is likely to play an important role in the pathogenesis of allergic conditions in humans. MCP-3 did not induce inflammatory cell influx into nasal mucosa. The role of this chemokine in the pathogenesis of allergic inflammation is difficult to assess and requires further studies.

Transduction of human MCP-3 by a parvoviral vector induces leukocyte infiltration and reduces growth of human cervical carcinoma cell xenografts.

BACKGROUND: The oncosuppressive properties of some autonomous parvoviruses such as H-1 virus, together with their low pathogenicity, make them attractive vectors for tumor-directed gene therapy. Indeed, it was recently shown that these viruses became endowed with an enhanced oncosuppressive activity after they had been engineered to deliver a recognized therapeutic transgene. This prompted us to use a parvoviral vector to analyse the antineoplastic capacity of MCP-3 (monocyte chemotactic protein-3), a CC chemokine which has a broad spectrum of target cells, and can thus be considered to be a promising candidate for cancer treatment. METHODS: We explored the use of a parvovirus H-1-based vector encoding human MCP-3 for its antitumor potential on human cervical carcinoma cells. HeLa cells were infected in vitro with the recombinant virus hH1/MCP-3 at a low multiplicity [1 replication unit (RU)/cell] and we investigated the effect of parvovirus-mediated MCP-3 transduction on tumor formation and growth upon implantation of HeLa cells in nude mice. RESULTS: Infection of HeLa cells with hH1/MCP-3 led to secretion of high levels of MCP-3 and to significant retardation of tumor growth in recipient mice, as compared with HeLa cells that were either buffer-treated or infected with a MCP-3-free vector. Tumors from hH1/MCP-3-infected HeLa cells were heavily infiltrated with activated macrophages and showed increased numbers of dendritic cells. In addition, activated natural killer (NK) cells were also recruited into MCP-3-transduced tumors. CONCLUSION: These observations indicate that parvovirus H-1-transduced MCP-3 is able to exert a significant antitumor activity which is mediated, at least in part, through macrophages and NK cells, under conditions in which activated T cells are lacking.