Regulation of cell‐surface receptors for hematopoietic differentiation‐inducing protein MGI‐2 on normal and leukemic myeloid cells

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Abstract
The normal myeloid hematopoietic regulatory proteins include 4 different growth‐inducing proteins (IL‐3, MGI‐1GM = GM‐CSF, MGI‐1G = G‐CSF, and MGI‐1M = M‐CSF = CSF‐1). There is also another type of normal myeloid regulatory protein (MGI‐2) with no MGI‐1 (CSF or IL‐3) activity, which can induce differentiation of normal myeloid precursors and certain clones of myeloid leukemic cells. Studies on the binding of MGI‐2 to differentiation‐competent (D+) and differentiation‐defective (D−) clones of mouse myeloid leukemic cells and to normal cells indicate that: (1) D+ clones of myeloid leukemic cells had about 2,500 high‐affinity surface receptors per cell, like mature normal myeloid cells, and the bound MGI‐2 was rapidly internalized with its cell‐surface receptors at 37°C causing down‐regulation of MGI‐2 receptors in both the normal and leukemic cells; (2) in some D− clones, the number and internalization of MGI‐2 receptors were similar to those of D+ clones whereas other D− clones had only 0–100 MGI‐2 receptors per cell; (3) normal thymus and lymph‐node lymphocytes and T lymphoma cells did not show detectable MGI‐2 receptors; (4) there was an independent expression of receptors for MGI‐2 and for the 4 myeloid growth‐inducing proteins on different clones of myeloid leukemic cells; and (5) none of the 4 myeloid growth‐inducing proteins IL‐3, MGI‐1GM, MGI‐1G, or MGI‐1M, inhibited binding of MGI‐2 to its receptors. The cytotoxic proteins lymphotoxin and tumor necrosis factor did not induce differentiation of the mouse myeloid leukemic cells and also did not inhibit binding of MGI‐2 to its receptors. These results show that the myeloid differentiation‐inducing protein MGI‐2 binds to cell‐surface receptors that are different from the receptors for the 4 myeloid growth‐inducing proteins and these cytotoxic proteins.