INCREASED AGITATION INTENSITY INCREASES CD13 RECEPTOR SURFACE CONTENTAND MESSENGER-RNA LEVELS, AND ALTERS THE METABOLISM OF HL60 CELLS CULTURED IN STIRRED-TANK BIOREACTORS

Flow cytometry and Northern blotting were used to examine the effects of hydrodynamic forces in stirred tank bioreactors on CD13 receptor su rface content and mRNA levels of HL60 (human promyelocytic leukemia) c ells. A step increase in agitation rate from 80 to 300 or 400 rpm redu ced the apparent HL60 growth rate in a dose-dependent manner. This ste p increase in agitation rate (to 300 or 400 rpm) also increased the CD 13 receptor surface content on average by 30% and 100%, respectively. This increase in CD13 receptor surface content was correlated with a 1 0% and a 60% increase in CD13 mRNA levels. We also observed a signific ant and very reproducible drop in CD13 expression over the course of a batch bioreactor run (80 rpm). Although we have no explanation for th is, we show that the decrease in CD13 receptor surface content can be (at least partially, if not fully) explained by the corresponding decr ease in CD13 mRNA. HL60 cell cultures agitated at 300 and 400 rpm exhi bited glucose consumption and lactate production rates that were appro ximately 40% and 90% greater than values of the cultures agitated at 8 0 rpm. The physiological and practical implications of these results a re discussed. (C) 1998 John Wiley & Sons, Inc.