HYALURONIC-ACID ENHANCES CELL-PROLIFERATION DURING EOSINOPOIESIS THROUGH THE CD44 SURFACE-ANTIGEN

We examined the effect oi hyaluronic acid in promoting proliferation o f undifferentiated progenitor cells through the CD44 receptor during e osinopoiesis in vitro. Undifferentiated umbilical cord blood cells wer e purified on the first day to isolate primitive progenitor cells expr essing the CD34 hemopoietic surface marker. Culture in wells coated wi th 100 mu g/ml hyaluronic acid caused a 198 +/- 28.7% augmentation of proliferation of CD34(+) progenitor. cells at 3 wk (p < 0.01). By cont rast, concentrations of hyaluronic acid >10 mu g/ml inhibited prolifer ation of unfractionated cord blood mononuclear cells. The augmented pr oliferation of precursor cells caused by hyaluronic acid was associate d with complete (93.0 +/- 5.12%) differentiation to eosinophil morphol ogy. By contrast, concentrations of hyaluronic acid greater than or eq ual to 10 mu g/ml inhibited eosinophilic differentiation of unfraction ated mononuclear cells. Wright-Giemsa staining demonstrated 95.4 +/- 2 .92% eosinophils for CD34(+) cells cultured for 3 wk without hyaluroni c acid (control) and 93.8 +/- 5.11% for CD34(+) cells cultured in hyal uronic acid-coated wells (100 mu g/ml); for unfractionated cells, 94.0 +/- 3.02% demonstrated eosinophilic morphology in control wells at 3 wk vs 55.4 +/- 8.34% in hyaluronic acid-coated (100 mu g/ml) wells (p < 0.05). Augmented proliferation caused by hyaluronic acid was attenua ted completely by the anti-CD44 mAbs, 212.3 and IM7.8.1. Pretreatment of CD34(+) cells with 5 mu g/ml 212.3 inhibited the augmented prolifer ation caused by the optimal concentration of hyaluronic acid (100 mu g /ml) from 260 +/- 39.2% of control growth to 114 +/- 16.4% of control growth (p = 0.02). Inhibition was comparable for IM7.8.1. Control mAb (LM2) to the beta(2) integrin subunit CD11b had no effect on prolifera tion induced by hyaluronic acid. We demonstrate that hyaluronic acid s timulates the growth of CD34(+) selected umbilical cord blood cells in to specifically differentiated mature eosinophils. This process is mod ulated by the CD44 receptor on the progenitor cell population.