FIBRONECTIN RESTORES DEFECTIVE IN VITRO PROLIFERATION OF... : Transplantation (original) (raw)

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FIBRONECTIN RESTORES DEFECTIVE IN VITRO PROLIFERATION OF PATIENTS' LYMPHOCYTES AFTER MARROW GRAFTING

The Fred Hutchinson Cancer Research Center and the University of Washington School of Medicine, Seattle, Washington

Dr. Klingemann was supportd by Grant 300/402/504/5 from Dr. Mildred Scheel Stiftung, FRG.

2Address correspondence to: Hans-Gorg Klingemann, Division of Hematology, Department of Medicine, University of British Columbia, 910 West 10th Avenue, Vancouver, B.C. V5Z 1MG.

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Abstract

In search for means of improving the impaired lymphocyte function of recipients after marrow grafting, we investigated the effect of fibronectin (FN) on patients' lymphocytes in allogeneic mixed lymphocyte cultures (MLC) and in cell-mediated lympholysis (CML) assays, since these tests are usually defective in transplanted patents. Four subgroups of marrow recipients were tested: patients within the first 100 days of transplantation (short-term) with (n=16) or without (n=14) acute graft-versus-host disease (GVHD), and long-term recipents with (n=23) or without (n=15) chronic GVHD. Exogenous FN (25 ug/ml) increased the proliferative response in the allogeneic mixed lymphocyte culture (MLC) significantly in cells from short-term patients without acute GVHD (+42%) and in those from long-term recipients with (+117%) and without chronic GVHD (+48%). In cells from patients with chronic GVHD, 3H-thymidine uptake after the addition of FN was enhanced to the level of that in lymphocytes of the corresponding marrow donor without exogenous FN. Fibronectin was effetive only if added at the beginning of the MLC. In contrast to the results in MLC, exogenous FN failed to enhance phytohemagglutinin or OKT-3-induced lymphocyte proliferation and had no effect on CML activity. Moreover, FN did not show mitogenic activity in 3–6-day cultures.

Our results demonstrate that FN in vitro is capable of restoring defective lymphocyte proliferation in marrow grafted patients, and circumstantial evidence suggests that this effect is mediated by an interaction between FN and monocytes.