Altered recruitment of Lyn, Syk and ZAP-70 into lipid rafts of activated B cells in Systemic Lupus Erythematosus
| Autor: | Blanca Ortiz-Reyes, Nursamaa Abdoel, Andres Baena, Mauricio Restrepo, Luis F. García, Gloria Vásquez, Ana María Vásquez, Mauricio Rojas, Adriana L. Vanegas-García, CH Muñoz, Luis Alonso González |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Cell signaling Syk Lymphocyte Activation 03 medical and health sciences Young Adult 0302 clinical medicine Membrane Microdomains LYN hemic and lymphatic diseases Calcium flux medicine Humans Lupus Erythematosus Systemic Syk Kinase skin and connective tissue diseases Lipid raft B cell B-Lymphocytes Systemic lupus erythematosus ZAP-70 Protein-Tyrosine Kinase business.industry breakpoint cluster region hemic and immune systems Cell Biology Middle Aged medicine.disease 030104 developmental biology medicine.anatomical_structure src-Family Kinases 030220 oncology & carcinogenesis Immunology Female business |
| Zdroj: | Cellular signalling. 58 |
| ISSN: | 1873-3913 |
| Popis: | There is evidence that B cells from patients with Systemic Lupus Erythematosus (SLE) could be hyperactivated due to changes in their lipid rafts (LR) composition, leading to altered BCR-dependent signals. This study aimed to characterize possible alterations in the recruitment of protein tyrosine kinases (PTK) into B cells LR from SLE patients. Fifteen patients with SLE and ten healthy controls were included. Circulating B cells were isolated by negative selection and stimulated with goat Fab´2 anti-human IgM/IgG. LR were isolated with a non-ionic detergent and ultracentrifuged on 5-45% discontinuous sucrose gradients. Proteins from each fraction were analyzed by Western Blot. Total levels of Lyn, Syk, and ZAP-70 in resting B cells were similar in SLE patients and healthy controls. Upon BCR activation, Lyn, Syk and ZAP-70 recruitment into LR increased significantly in B cells of healthy controls and patients with inactive SLE. In contrast, in active SLE patients there was a great heterogeneity in the recruitment of signaling molecules and the recruitment of ZAP-70 was mainly observed in patients with decreased Syk recruitment into LR of activated B cells. The reduction in Flotilin-1 and Lyn recruitment in SLE patients seem to be associated with disease activity. These findings suggest that in SLE patients the PTK recruitment into B cell LR is dysregulated and that B cells are under constant activation through BCR signaling. The decrease of Lyn and Syk, the expression of ZAP-70 by B cells and the increase in Calcium fluxes in response to BCR stimulation in active SLE patients, further support that B cells from SLE patients are under constant activation through BCR signaling, as has been proposed. |
| Databáze: | OpenAIRE |
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