MODIFICATIONS IN THE SYNTHESIS OF MEMBRANE-ASSOCIATED CHONDROITIN SULFATE PROTEOGLYCANS IN HEMATOPOIETIC PROGENITOR CELLS ARE ACCOMPANIED BY ALTERATIONS IN THEIR ADHESIVE PROPERTIES

In vitro studies in our laboratory have indicated that murine hemopoie tic progenitor cell (HPC) lines, irrespective of their differentiation stage, synthesize and accumulate in the cell membrane a unique specie s of chondroitin sulfate proteoglycan (CS-PG). It has been postulated that CS-PG participates in HPC adhesion to pericellular stromal fibron ectin by interacting with its heparin-promoting binding region. To fur ther support this contention, we first attempted to modify CS-PG synth esis in HPC by the use of chlorate and p-nitrophenyl beta-D-xyloside, which inhibit sulfation and glycosaminoglycan (GAG) addition in proteo glycans, respectively. We then studied the effect that these modificat ions may have in the adhesive capacity of HPC to interact with fibrone ctin and its cell- and heparin-promoting binding chymotryptic fragment s. Treatment with chlorate which resulted in a decreased sulfation of membrane-associated 35 S-labeled CS-PG, as judged by ion exchange chro matography, did not affect HPC adhesion to fibronectin or its fragment s. However, beta-xyloside treatment which reduces the abundance of mem brane-associated CS-PG, as evidenced by molecular sieve chromatography , produced a major and specific decrease in HPC adhesion to the hepari n-promoting binding fragment of fibronectin. These results indicate th at CS-PG are involved in HPC interaction with fibronectin, in a mode t hat seems to be dependent on the differentiation stage of HPC. (C) 199 4 Wiley-Liss, Inc.