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Implication of CD44 in adhesion‐mediated overproduction of TGF‐β and IL‐1 in monocytes from patients with bone marrow fibrosis
Author(s) -
Rameshwar Pranela,
Chang Victor T.,
Gascón Pedro
Publication year - 1996
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1996.4631004.x
Subject(s) - extracellular matrix , fibronectin , cell adhesion molecule , cd44 , fibrosis , osteopontin , chemistry , bone marrow , microbiology and biotechnology , immunology , biology , medicine , pathology , biochemistry , cell
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 overactivates 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‐β 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‐β and IL‐1 produced. Immunoprecipitation of CD44 revealed three proteins at approximately 110 kD in MF monocytes and one in NC. Our results indicate that adhesion is important in overproduction of TGF‐β 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 BM fibrosis.