Accessory cells mediate hairy-cell proliferation by mechanism(s) involving both adhesion and TNF alpha secretion.
The mechanisms responsible for hairy-cell (HC) growth both in vitro and in vivo are still unclear. In a recent study we showed that monocytes/macrophages induce HC proliferation in vitro. The purpose of the present paper is to examine the specificity of this accessory cell effect and to establish the mechanism(s) involved. We demonstrate that the effect is not confined to monocytes/macrophages but is also potentially seen with a range of other cell types. However, at low accessory cell:HC ratios (< 1:20) only human umbilical vein endothelial cells (HUVEC) and macrophages induce HC proliferation. We suggest that these observations are of pathophysiological significance in relation to the close association frequently observed between HCs and endothelial cells/macrophages in the liver and spleen of patients with hairy-cell leukaemia (HCL). Regarding the mechanisms of the accessory cell effect, we show that both soluble factors and cell contact are important. A blocking anti-TNF alpha antibody abrogated the HC proliferation induced by HUVEC supernatant, indicating the involvement of this cytokine. Interaction of HCs with HUVEC via CD11b and 11c leucocyte integrins was shown to be important in the contact effect. Our demonstration of the involvement of both cytokines and cell contact in HC proliferation is in accord with what is already known about the control of B-cell growth and differentiation. More specifically, our results suggest that TNF alpha and interaction with endothelial cells/macrophages via leucocyte integrins are involved in the proliferation of late B-cells of the maturational stage represented by HCs.
Till
K J
KJ
Department of Haematology, Royal Liverpool University Hospital.
Cawley
J C
JC
D000938:Antigen-Presenting Cells / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology*; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000502:physiology; D007943:Leukemia, Hairy Cell / Q000473:pathology*; D008264:Macrophages / Q000502:physiology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D016023:Integrins; D014409:Tumor Necrosis Factor-alpha