Signal transduction events in human peripheral blood mononuclear cells stimulated by Schistosoma mansoni antigens.
Activation of protein tyrosine kinases (PTKs) is a common step of T cell stimulation. However, the relationship between PTKs and activation of peripheral blood mononuclear cells (PBMC) from intestinal chronic schistosomiasis patients has not been explored yet. In this study, we investigated the participation of Lck and ZAP-70 protein tyrosine kinases (PTKs), as well as PLC-gamma1 and Shc proteins in PBMC activation by Schistosoma mansoni antigens. PBMC were stimulated with SEA (soluble egg antigen) or SWAP (soluble worm preparation), lysed, precipitated with specific antibodies and the level of tyrosine phosphorylation evaluated. Our results show that Lck and Shc were phosphorylated upon stimulation of the cells with SWAP, as well as with SEA. However, the phosphorylation level was more pronounced in SWAP than in SEA-stimulated cells. Phosphorylation of ZAP-70 was observed only in SWAP stimulated cells. Additionally, PLC-gamma1 phosphorylation was not observed in PBMC stimulated with SEA. Together, these results indicate that SEA and SWAP induce PBMC proliferation through distinct intracellular signaling pathways. Moreover, the weaker response of PBMC to SEA compared to SWAP stimulation suggests down-regulation of cells from intestinal chronic schistosomiasis patients to SEA, which may occur during immunomodulation to S. mansoni response.
Almeida
C A
CA
Departamento de Bioquimica e Imunologia, Universidade Federal de Minas Gerais, ICB, MG, Belo Horizonte, Brazil.
Leite
M F
MF
Goes
A M
AM
D000818:Animals; D000947:Antigens, Helminth / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D007411:Intestinal Diseases, Parasitic / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D008213:Lymphocyte Activation / Q000276:immunology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D051966:Phospholipase C gamma; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D051746:ZAP-70 Protein-Tyrosine Kinase; D019061:src-Family Kinases / Q000378:metabolism
D000947:Antigens, Helminth; D016207:Cytokines; D007527:Isoenzymes; D011948:Receptors, Antigen, T-Cell; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D019061:src-Family Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma