Anna Ziolkowska

Liver sinusoidal blood containing natural killer-like cells.

Rat liver sinusoidal washout cells were examined. These cells, which arc marginated in sinusoids, could he washed out by simple flushing of the vasculature with culture media without enzymes and under physiological portal pressure. They revealed, in comparison to peripheral blood mononuclear cells, which cytotoxic activity commonly attributed to the natural killer (SK) and natural cytotoxic (NC) cells, and were found to be anti‐asialo‐GM1‐negative. Liver sinusoidal Cytotoxic cell (LSCC) activity has been found to be associated with the large granular lymphocytes in low‐density cells in OX8‐positive as well as in OX8‐negative populations. The mononuclear cells washed out from the liver microvasculature could be stimulated with NK‐sensitive targets to release soluble factors which selectively lyse YAC‐I tumour cells and inhibit growth of normal haematopoietic granulocyte‐macrophage colony‐forming cells in vitro. The cytotoxic cell population in the liver turned out to be blood‐borne in origin and not resident Our findings suggest that liver sinusoidal cytotoxic cells represent an NK population with a predilection for marginating in the liver and may be important in eliminating tumour or virus infected cells passing through the liver from the circulation. The mechanism of their accumulation in liver sinusoids remains unclear.

Vascularized bone marrow transplanted in orthotopic hind-limb stimulates hematopoietic recovery in total-body-irradiated rats.

Abstract Hematopoietic recovery after bone marrow transplantation (BMT) is reported to be slow with long‐lasting immune deficiency. This may be attributable to lack of a proper microenvironment for hematopoietic cell proliferation and differentiation. We have designed a model in which complete hematopoietic reconstitution of lethally irradiated rats can be achieved by vascularized bone marrow transplantation (VBMT) in an orthotopic hind‐limb graft. The aim of the study was to investigate the process of repopulation of bone marrow cavities and peripheral blood of irradiated rats after VBMT and, in particular, to follow the contribution of grafted BM cells and residual recipient BM cells in hematopoietic regeneration. Lewis hind‐limbs were transplanted orthotopically to totally irradiated (8 Gy) syngeneic sex‐mismatched recipients (VBMT). In the control group 8 × 107 BM cells in suspension were injected intravenously (BMCT). After 10 days BM and peripheral blood (PB) cells were collected from the recipient. For cell subset analysis cytomorphological evaluation of BM smears and flow cytometry of PB cells were performed. Additionally, PCR was performed using specific primers for rat Y chromosome (sex‐determining region Y‐Sry) to detect male (donor or recipient) cells in sex‐mismatched BM graft recipients and the products were analyzed by electrophoresis. VBMT brought about much faster replenishment of nucleated cells in BM and PB than did BMCT. Cytometry analysis of PB cells revealed more lymphocytes in VBMT than in BMCT recipients. The amount of donor DNA of bands corresponding to Y‐Sry was also higher in PB cells of VBMT than of BMCT recipients. The presence of host DNA was observed in PB cells of VBMT rats but was not detected in PB population of BMCT recipients. VBMT is highly effective in hematopoietic reconstitution of irradiated recipients. The fast cell maturation and repopulation may be due to the presence of stromal cells transplanted in a normal spatial relationship with donor hematopoietic cells in hind‐limb graft. Self renewal of radioresistant host cells was seen after VBMT but not after BMCT.