Granulocyte macrophage colony-stimulating activity production by cultured human thymic nonlymphoid cells is regulated by endogenous interleukin-1.
Supernatants of cultured human thymic nonlymphoid cells were assayed for granulopoietic factors using cultures of low density bone marrow mononuclear cells (LD-BMMC). Thymic nonlymphoid cell-conditioned medium (TNLC-CM) supported vigorous myeloid colony growth of LD-BMMC, and of LD-BMMC depleted of T lymphocytes and/or monocytes. Colony stimulating activity (CSA) in TNLC-CM was abrogated by a highly specific neutralizing antiserum against recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). TNLC-CM also enhanced colony growth in LD-BMMC stimulated by colony stimulating activity from a giant cell tumor culture (GCT). The enhancing activity of TNLC-CM, unlike its CSA activity, required the presence of adherent cells in the marrow cell culture. The addition of anti-interleukin-1 (anti-IL-1) antibody to TNLC-CM inhibited the GCT-enhancing activity, but not the CSA. When the anti-IL-1 immunoglobulin was added directly to cultures of thymic nonlymphoid cells, GM-CSF production was completely inhibited, and the GCT enhancing activity was neutralized. We conclude that an intercellular regulatory network exists in cultured thymic explants in which GM-CSF expression is induced by IL-1. In this system, the granulopoietic effect of IL-1 derives not from a direct effect on myeloid progenitors, but from its ability to recruit CSA production by other cells.
D000911:Antibodies, Monoclonal / Q000502:physiology; D001854:Bone Marrow Cells; D002452:Cell Count; D002469:Cell Separation; D002478:Cells, Cultured; D002675:Child, Preschool; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000096:biosynthesis* / Q000276:immunology; D003470:Culture Media / Q000502:physiology; D004357:Drug Synergism; D005870:Giant Cell Tumors / Q000032:analysis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007375:Interleukin-1 / Q000276:immunology / Q000502:physiology*; D009000:Monocytes; D013601:T-Lymphocytes; D013950:Thymus Gland / Q000166:cytology*
D000911:Antibodies, Monoclonal; D003115:Colony-Stimulating Factors; D003470:Culture Media; D006133:Growth Substances; D007106:Immune Sera; D007375:Interleukin-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor