Transforming growth factor beta 1 systemically modulates granuloid, erythroid, lymphoid, and thrombocytic cells in mice.
Transforming growth factor beta 1 (TGF-beta 1) has been shown to inhibit the development of most early hemopoietic progenitors in vitro. The present series of in vivo experiments show that TGF-beta 1 can simultaneously augment and suppress distinct cell lineages in peripheral and central hemopoietic compartments. Mice treated daily for 7-14 days with s.c. injections of TGF-beta 1 exhibited up to a 95% reduction in circulating platelets and a 50% reduction in red cell counts, whereas a 50%-400% increase occurred in circulating white cells with the morphology of small lymphocytes. Decreased erythrocytes were also evident in the splenic red pulp and bone marrow sinusoids. A dramatic increase in granulopoiesis occurred in the spleen and bone marrow, followed by a peripheral neutrophilia 1 week after treatments ceased. All effects were completely reversible, with normal histologic and hematologic profiles evident 2 weeks after cessation of treatments. Thus, TGF-beta 1 can differentially regulate multiple hemopoietic pathways in a systemic, reversible, and dose-dependent fashion. These actions may be mediated by the direct effects of TGF-beta 1 or through modulation of secondary cytokines and receptors.
Carlino
J A
JA
Department of Immunology, Celtrix Laboratories, Incorporated, Palo Alto, California 94303.
Higley
H R
HR
Creson
J R
JR
Avis
P D
PD
Ogawa
Y
Y
Ellingsworth
L R
LR
D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects; D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004906:Erythrocyte Count / Q000187:drug effects; D004912:Erythrocytes / Q000166:cytology* / Q000187:drug effects; D006098:Granulocytes / Q000166:cytology* / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D007279:Injections, Subcutaneous; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010976:Platelet Count / Q000187:drug effects; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology*
D016212:Transforming Growth Factor beta