Activation of MAPK Is Required for ROS Generation and Exocytosis in HMC-1 Cells Induced by Trichomonas vaginalis-Derived Secretory Products

Trichomonas vaginalis is a flagellated protozoan parasite that causes vaginitis and cervicitis in women and asymptomatic urethritis and prostatitis in men. Mast cells have been reported to be predominant in vaginal smears and vaginal walls of patients infected with T. vaginalis. Mitogen-activated protein kinase (MAPK), activated by various stimuli, have been shown to regulate the transcriptional activity of various cytokine genes in mast cells. In this study, we investigated whether MAPK is involved in ROS generation and exocytotic degranulation in HMC-1 cells induced by T. vaginalis-derived secretory products (TvSP). We found that TvSP induces the activation of MAPK and NADPH oxidase in HMC-1 cells. Stimulation with TvSP induced phosphorylation of MAPK and p47phox in HMC-1 cells. Stimulation with TvSP also induced up-regulation of CD63, a marker for exocytosis, along the surfaces of human mast cells. Pretreatment with MAPK inhibitors strongly inhibited TvSP-induced ROS generation and exocytotic degranulation. Finally, our results suggest that TvSP induces intracellular ROS generation and exocytotic degranulation in HMC-1 via MAPK signaling.

Evolutionary conservation of laminin-binding proteins

The virulence of pathogens and metastatic capacity of cancer cells seems to correlate with the ability to adhere to cells and/or to basement components. A key feature of this mechanism in the expression of specific receptors for the basement membrane protein laminin. There different receptors have been already described in cells phylogenetically very distant, such as human white blood cells, Trichomonas vaginalis and Stapgylococcus aureus, all recognizing laminin with the same range of affinity. We have shown that laminin, which is also found in the circulation, enchances phagocytosis of S. aureus by macrophages in a species-specific fashion. Also, monoclonal antibodies (MAb) raised against the bacterial receptor inhibit the phagocytic enhancement mediated by laminin and recognize laminin-binding proteins in unicellular parasites and mammalian cells. The same Mab 1.H12 elutes a 52-kDa protein from bacterial extracts and a 67-kDa band from cancer cells extracts. Since the MAb is a monospecific reagent, results with 1.H12 strongly suggest and evolutionary conservation of the biding site of phylogenetically different laminin receptors