Heparan sulphate proteoglycans (HSPGs) present on the surface of bone marrow stromal cells and in the extracellular matrix (ECM) have important roles in the control of adhesion and growth of haemopoietic stem and progenitor cells. The two main groups of proteoglycans which contain heparan sulphate chains are members of the syndecan and glypican families. In this study we have identified the main surface membrane and matrixassociated HSPGs present in normal human bone marrow stroma formed in long-term culture. Proteoglycans were extracted from the adherent stromal layers and treated with heparitinase and chondroitinase ABC. The core proteins were detected by Western blotting using antibodies directed against syndecans-1-4, glypican-1 and the ECM HSPG, perlecan. Stromal cell expression at the RNA level was detected by Northern blotting and by reverse transcription PCR. Glypican-1, syndecan-3 and syn-
SUMMARY Serial monitoring of the serum C-reactive protein (CRP) concentration was performed, using a one-hour laser-immunonephelometric assay, during 29 episodes of infection in 22 neutropenic patients with acute leukaemia. Serum CRP increased to above a diagnostic level of 100 mg/l in all 29 episodes and continued to rise progressively until appropriate antibiotics, or granulocytes, were given when it fell with a half-life of approximately three days. Serial study of the serum concentration was of value in detecting occult or unresolved bacterial infection and provided an objective means of monitoring the response to antibiotic and granulocyte therapy.Infection, when unrecognised or treated ineffectively, is the commonest cause of death in neutropenic patients with acute leukaemia. Because of the lack of granulocytes, clinical and radiological signs of infection are often inadequate and the diagnosis of potentially-fatal infection may be delayed. Empirical treatment with a broad-spectrum antibiotic combination, given intravenously, may be life saving but there are few objective guidelines to indicate when bacterial infection is responding and for how long intravenous antiobiotics should be continued. An objective method for quantifying the inflammatory response might therefore be of clinical value in guiding antibiotic policy and indicating when granulocytes should be given. ' Acute infection, and other causes of an inflammatory response, will induce hepatic synthesis2 of C-reactive protein (CRP) and other acutephase reactant proteins so that a rise in serum concentration occurs within a few hours or days.3 C-reactive protein has been widely studied as an acute-phase reactant4 and the rise in serum concentration may be detected within one hour of experimentally-induced endotoxaemia.5 Rapid measurement of CRP is now possible using laser immunonephelometric6 or rate immunonephelometric7 assays and the present study was designed to investigate the value of the one-hour laser immunonephelometric assay as a guide to the effectiveness of antibiotic therapy in acute leukaemia.
Highly regulated interactions between adhesion receptors on progenitor cells and their extracellular matrix ligands are essential for the control of hematopoiesis in bone marrow stroma. We have examined the relationship between α4β1-integrin–mediated adhesion and growth of CD34+ cells by assessing their adhesive and migratory patterns of proliferation in a mixture of hematopoietic growth factors in the presence of different recombinant fragments of theHepII/IIICS region of fibronectin. CD34+ cells were isolated from cord blood and placed in culture wells containing serum-free medium and growth factors. Wells were precoated with either the H120 fragment of fibronectin, which contains three α4β1-integrin binding sites, or the H0 fragment, which lacks the two highest affinity α4β1 binding sequences. Proliferation of single cells of CD34+38+DR+and CD34+38−DR+ phenotypes occurred in contact with the H120 substrate and was associated with migration. Larger numbers of cells were used to quantitate proliferative responses. Cells growing in wells coated with H120 formed attachments to the base of the wells throughout the culture period. Higher total cell counts were consistently found in wells coated with H120 compared with H0 and bovine serum albumin controls. The difference was first apparent at day 8 of culture and reached a maximum at days 11 through 13, when expansion with H120 was a mean of 1.8-fold higher than that seen with H0 (P≤ .0001). The greatest expansion (2.25-fold) with H120 compared with H0 was seen when the growth factor concentrations were reduced to 1/16 of the standard levels (P ≤ .001). The increase in total cell numbers was not at the expense of CD34+ cells as numbers of these were similar in H120 and control cultures. These results provide evidence for synergy between growth factors and integrins that may be relevant to understanding hematopoiesis in marrow stroma.
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