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Br J Haematol. 1996 Apr;93(1):22-9.

Implication of CD44 in adhesion-mediated overproduction of TGF-beta and IL-1 in monocytes from patients with bone marrow fibrosis.

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1
Department of Medicine, UMDNJ-New Jersey Medical School, Newark 07103, USA.

Abstract

Myelofibrosis (MF) is characterized by bone marrow (BM) fibrosis and excessive deposits of extracellular matrix (ECM) proteins which include fibronectin (FN), collagen type I and hyaluronic acid (HA). We have previously reported that adhesion to polystyrene over-activates MF monocytes. We now confirm their activation by increased CD25 expression and tyrosine phosphorylation. We hypothesize that ECM protein-adhesion molecule interactions induce overproduction of fibrogenic cytokines in MF monocytes leading to BM fibrosis. In this study we found that FN, collagen type I and HA induce 2-3-fold more TGF-beta and 6-9 fold more interleukin (IL)-1 in MF monocytes than normal controls (NC). Since CD44 can function as the natural ligand for these proteins, its role was studied. We found that CD44 mediated most of the TGF-beta and IL-1 produced. Immunoprecipitation of CD44 revealed three proteins at approximately 11 kD in MF monocytes and one in NC. Our results indicated that adhesion is important in overproduction of TGF-beta and IL-1, and that their production is at least partly mediated by adhesion molecule-ECM protein interactions. These results implicate at least one adhesion molecule, CD44, in the pathophysiology of the BM fibrosis.

[Indexed for MEDLINE]

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