Hyaluronic acid enhances cell proliferation during eosinopoiesis through the CD44 surface antigen

We examined the effect of hyaluronic acid in promoting proliferation of undifferentiated progenitor cells through the CD44 receptor during eosinopoiesis in vitro. Undifferentiated umbilical cord blood cells were purified on the first day to isolate primitive progenitor cells expressing the CD34 hemopoietic surface marker. Culture in wells coated with 100 micrograms/ml hyaluronic acid caused a 198 +/- 28.7% augmentation of proliferation of CD34+ progenitor cells at 3 wk (p < 0.01). By contrast, concentrations of hyaluronic acid > 10 micrograms/ml inhibited proliferation of unfractionated cord blood mononuclear cells. The augmented proliferation of precursor cells caused by hyaluronic acid was associated with complete (93.0 +/- 5.12%) differentiation to eosinophil morphology. By contrast, concentrations of hyaluronic acid > or = 10 micrograms/ml inhibited eosinophilic differentiation of unfractionated mononuclear cells. Wright-Giemsa staining demonstrated 95.4 +/- 2.92% eosinophils for CD34+ cells cultured for 3 wk without hyaluronic acid (control) and 93.8 +/- 5.11% for CD34+ cells cultured in hyaluronic acid-coated wells (100 micrograms/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 micrograms/ml) wells (p < 0.05). Augmented proliferation caused by hyaluronic acid was attenuated completely by the anti-CD44 mAbs, 212.3 and IM7.8.1. Pretreatment of CD34+ cells with 5 micrograms/ml 212.3 inhibited the augmented proliferation caused by the optimal concentration of hyaluronic acid (100 micrograms/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 proliferation induced by hyaluronic acid. We demonstrate that hyaluronic acid stimulates the growth of CD34+ selected umbilical cord blood cells into specifically differentiated mature eosinophils. This process is modulated by the CD44 receptor on the progenitor cell population.