Granulocyte macrophage colony-stimulating activity production by cultured
human thymic nonlymphoid cells is regulated by endogenous interleukin-1
D Ridgway, MS Borzy and GC Bagby
Department of Pediatrics, Doernbecher Memorial Hospital, Portland, OR
97201.
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.
Volume 72,
Issue 4,
pp. 1230-1236,
10/01/1988
Copyright © 1988 by The American Society of Hematology
