Increased serum levels of transforming growth factor beta-1 in patients affected by thrombotic thrombocytopenic purpura (TTP): its implications on bone marrow haematopoiesis.
In this study we evaluated the effect of serum collected from seven thrombotic thrombocytopenic purpura (TTP) patients, either in the acute phase of the disease or in clinical remission, on the in vitro growth of bone marrow haematopoietic progenitor cells, obtained from the same TTP patients in clinical remission and from normal donors. The addition to the cultures of autologous sera collected from TTP patients in acute phase of the disease showed a clear-cut dose-dependent inhibition of immature haematopoietic progenitor cells (BFU-E, CFU-meg and 14th day CFU-GM). On the other hand, no inhibitory effects were observed on more mature 7th day CFU-GM. Interestingly, also sera collected from TTP patients in clinical remission still maintained some inhibitory activity on the growth of immature progenitor cells. A similar inhibitory activity was noticed when TTP sera were tested on normal bone marrow haematopoietic progenitor cells. Such inhibitory activity was significantly reduced in blocking experiments by the addition of a polyclonal neutralizing anti-TGF-beta 1 antibody and the presence of increased levels of both bioactive and latent TGF-beta 1 in TTP sera was confirmed in a bioassay on CCL64 cells. These data contribute to explain the lack of a clear compensatory haematopoiesis observed in some patients with active TTP and add further evidence to the notion of the existence of a state of latent platelet activation in TTP patients in clinical remission.
Zauli
G
G
Institute of Human Anatomy, University of Ferrara, Italy.
Gugliotta
L
L
Catani
L
L
Vianelli
N
N
Borgatti
P
P
Belmonte
M M
MM
Tura
S
S
D000208:Acute Disease; D000328:Adult; D001853:Bone Marrow / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D008297:Male; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood*; D016212:Transforming Growth Factor beta / Q000097:blood*
D016212:Transforming Growth Factor beta