Defective Chemokine-Directed Lymphocyte Migration and Development in the Absence of Rho Guanosine Diphosphate-Dissociation Inhibitors α and β
| Autor: | Hiroyoshi Ishizaki, Miyuki Nishimura, Atsushi Togawa, Miki Tanaka-Okamoto, Akiko Hamaguchi, Toshio Imai, Yoshimi Takai, Jun Miyoshi, Keiko Hori |
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| Rok vydání: | 2006 |
| Předmět: |
Male
rho GTP-Binding Proteins Chemokine RHOA T-Lymphocytes Lymphocyte Immunology Cell Count Mice Inbred Strains RAC1 Thymus Gland CDC42 Minor Histocompatibility Antigens Mice rho Guanine Nucleotide Dissociation Inhibitor beta medicine Animals rho-Specific Guanine Nucleotide Dissociation Inhibitors Immunology and Allergy Cytoskeleton Cells Cultured Guanine Nucleotide Dissociation Inhibitors rho Guanine Nucleotide Dissociation Inhibitor alpha B-Lymphocytes biology Chemotaxis CCL19 Proteins Marginal zone Cell biology medicine.anatomical_structure Organ Specificity biology.protein Lymph Nodes Spleen |
| Zdroj: | The Journal of Immunology. 177:8512-8521 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Rho family small GTP-binding proteins, including Rho, Rac, and Cdc42, are key determinants of cell movement and actin-dependent cytoskeletal morphogenesis. Rho GDP-dissociation inhibitor (GDI) α and Rho GDIβ (or D4/Ly-GDI), closely related regulators for Rho proteins, are both expressed in hemopoietic cell lineages. Nevertheless, the functional contributions of Rho GDIs remain poorly understood in vivo. In this study, we report that combined disruption of both the Rho GDIα and Rho GDIβ genes in mice resulted in reduction of marginal zone B cells in the spleen, retention of mature T cells in the thymic medulla, and a marked increase in eosinophil numbers. Furthermore, these mice showed lower CD3 expression and impaired CD3-mediated proliferation of T cells. While B cells showed slightly enhanced chemotactic migration in response to CXCL12, peripheral T cells showed markedly reduced chemotactic migration in response to CCL21 and CCL19 associated with decreased receptor levels of CCR7. Overall, Rho protein levels were reduced in the bone marrow, spleen, and thymus but sustained activation of the residual part of RhoA, Rac1, and Cdc42 was detected mainly in the bone marrow and spleen. Rho GDIα and Rho GDIβ thus play synergistic roles in lymphocyte migration and development by modulating activation cycle of the Rho proteins in a lymphoid organ-specific manner. |
| Databáze: | OpenAIRE |
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