Macrophage Migration Inhibitory Factor Is Up-Regulated in Human First-Trimester Placenta Stimulated by Soluble Antigen of Toxoplasma gondii , Resulting in Increased Monocyte Adhesion on Villous Explants

• Published in: The American journal of pathology Vol. 172; no. 1; pp. 50 - 58
• Main Authors: Ferro, Eloisa Amália Vieira, Mineo, José Roberto, Ietta, Francesca, Bechi, Nicoletta, Romagnoli, Roberta, Silva, Deise Aparecida Oliveira, Sorda, Giuseppina, Bevilacqua, Estela, Paulesu, Luana Ricci
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 2008; ASIP; American Society for Investigative Pathology
• Subjects: Animals; Biological and medical sciences; Cell Adhesion; Chorionic Villi - metabolism; Culture Media - metabolism; Female; Human protozoal diseases; Humans; Infectious diseases; Intercellular Adhesion Molecule-1 - metabolism; Interferon-gamma - metabolism; Investigative techniques, diagnostic techniques (general aspects); Macrophage Migration-Inhibitory Factors - biosynthesis; Macrophage Migration-Inhibitory Factors - physiology; Medical sciences; Monocytes - cytology; Monocytes - parasitology; Parasitic diseases; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Placenta - metabolism; Pregnancy; Pregnancy Trimester, First; Protozoal diseases; Recombinant Proteins - metabolism; Regular; Toxoplasma - metabolism; Toxoplasma gondii; Toxoplasmosis; Human; Protozoa; Apicomplexa; Protozoal disease; Monocyte; Fetal membrane; Explant; First trimester; Parasitosis; Soluble form; Adhesion; Infection; Antigen; Pregnancy; Macrophage migration inhibitory factor; Anatomic pathology; Regulation(control); Placenta; Toxoplasma gondii; Toxoplasmosis
• ISSN: 0002-9440; 1525-2191
• DOI: 10.2353/ajpath.2008.070432

Considering the potential role of macrophage migration inhibitory factor (MIF) in the inflammation process in placenta when infected by pathogens, we investigated the production of this cytokine in chorionic villous explants obtained from human first-trimester placentas stimulated with soluble antigen from Toxoplasma gondii (STAg). Parallel cultures were performed with villous explants stimulated with STAg, interferon-γ (IFN-γ), or STAg plus IFN-γ. To assess the role of placental MIF on monocyte adhesiveness to human trophoblast, explants were co-cultured with human myelomonocytic THP-1 cells in the presence or absence of supernatant from cultures treated with STAg (SPN), SPN plus anti-MIF antibodies, or recombinant MIF. A significantly higher concentration of MIF was produced and secreted by villous explants treated with STAg or STAg plus IFN-γ after 24-hour culture. Addition of SPN or recombinant MIF was able to increase THP-1 adhesion, which was inhibited after treatment with anti-MIF antibodies. This phenomenon was associated with intercellular adhesion molecule expression by villous explants. Considering that the processes leading to vertical dissemination of T. gondii remain widely unknown, our results demonstrate that MIF production by human first-trimester placenta is up-regulated by parasite antigen and may play an essential role as an autocrine/paracrine mediator in placental infection by T. gondii.