![]() For instance, SDF-1, BCA-1, and the liver and activation-regulated chemokine (LARC) are expressed in the liver. 5, 6 Also, chemokines are constitutively produced in nonhematopoietic tissues. 2-4 Furthermore, stromal cell–derived factor-1 (SDF-1) and its receptor CXCR4 are required for homing of progenitor cells to the bone marrow. Both receptors control lymphocyte trafficking in lymph nodes. The secondary lymphoid tissue chemokine (SLC) acts on the chemokine receptor CCR7, and the B-cell–attracting chemokine–1 (BCA-1) acts on the CXCR5 receptor. In addition, certain chemokines are constitutively expressed in hematopoietic and lymphoid tissues in which they regulate the migration and recirculation of various types of blood cells. 1 The synthesis of these factors is induced by proinflammatory cytokines. The influx of leukocytes into inflamed tissues is induced by chemoattractants including small peptides called chemokines, such as interleukin 8 (IL-8) and monocyte chemoattractant protein–1 (MCP-1). This indicates that the influx of these myeloid cells into all tissues requires the Gq/11 protein in addition to the Gi protein in the liver and spleen. In contrast, overexpression of a function-defective mutant of the Gq/11 protein blocked dissemination to the bone marrow and also prevented Gq/11 dissemination to the liver and spleen. ![]() ![]() Pertussis toxin S1 blocked dissemination of MDAY-D2 murine myeloid leukemia cells to the liver and spleen, as in T-cell hybridoma cells, but it did not prevent bone marrow colonization. In fact, dissemination of a T-cell hybridoma, a model for T lymphoma, was blocked when Gi proteins were inactivated by the S1 catalytic subunit of pertussis toxin that had been transfected into those cells. It seems likely that the colonization of tissues during dissemination of hematopoietic tumor cells is similarly regulated. The migration of leukocytes into tissues is regulated by chemokines and other chemotactic factors that act on receptors that signal through Gi proteins.
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