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Elevated pCO\n                    <jats:sub>2<\/jats:sub>\n                    and osmolality inhibit hybridoma growth to similar extents in both serum\u2010containing and serum\u2010free media. The combination of osmolality and elevated pCO\n                    <jats:sub>2<\/jats:sub>\n                    synergizes to negatively impact cell growth. IgG\n                    <jats:sub>2a<\/jats:sub>\n                    glycosylation by hybridoma cells was evaluated under elevated pCO\n                    <jats:sub>2<\/jats:sub>\n                    (to 250 mmHg pCO\n                    <jats:sub>2<\/jats:sub>\n                    ) and\/or osmolality (to 476 mOsm\/kg). IgG\n                    <jats:sub>2a<\/jats:sub>\n                    site occupancy did not change significantly under any of the conditions studied, which is consistent with the robust glycosylation of other antibodies produced under various environmental stresses. However, changes were observed in the IgG\n                    <jats:sub>2a<\/jats:sub>\n                    charge distribution. Changes in the isoelectric point (pI) were greater under hyperosmotic stress, increasing by 0.32 and 0.41 pH units at 435 mOsm\/kg in serum\u2010containing and serum\u2010free medium, respectively. Hyperosmotic stress also resulted in a concomitant increase in the heterogeneity of the charge distribution. The mean pI in serum\u2010containing medium decreased by 0.16 pH units at 250 mmHg pCO\n                    <jats:sub>2<\/jats:sub>\n                    when osmolality was controlled at 320 mOsm\/kg but increased by 0.20 pH units when the osmolality increased with pCO\n                    <jats:sub>2<\/jats:sub>\n                    (195 mmHg pCO\n                    <jats:sub>2<\/jats:sub>\n                    \u2013435 mOsm\/kg). In serum\u2010free medium, elevated pCO\n                    <jats:sub>2<\/jats:sub>\n                    did not alter pI, regardless of medium osmolality. In contrast to elevated osmolality at control pCO\n                    <jats:sub>2<\/jats:sub>\n                    , elevated pCO\n                    <jats:sub>2<\/jats:sub>\n                    did not significantly alter the IgG\n                    <jats:sub>2a<\/jats:sub>\n                    charge heterogeneity under any of the conditions studied. The IgG\n                    <jats:sub>2a<\/jats:sub>\n                    was not sialylated, so sialylation changes were not responsible for changes in the charge distribution. IgG\n                    <jats:sub>2a<\/jats:sub>\n                    galactose content decreased with elevated osmolality, as a result of either elevated NaHCO\n                    <jats:sub>3<\/jats:sub>\n                    or NaCl. However, when osmolality was controlled at elevated pCO\n                    <jats:sub>2<\/jats:sub>\n                    , the galactose content tended to increase. The mannose content decreased with increasing stress, while the fucose content remained relatively unchanged. It is likely that the observed increases in the pI of murine IgG\n                    <jats:sub>2a<\/jats:sub>\n                    were due to increased organellar pH, which is reflected by increased specific \u03b2\u2010galactosidase activity in the supernatant.\n                  <\/jats:p>","DOI":"10.1021\/bp010187d","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T02:08:28Z","timestamp":1027649308000},"page":"346-353","source":"Crossref","is-referenced-by-count":50,"title":["Hyperosmotic Stress and Elevated pCO\n                    <sub>2<\/sub>\n                    Alter Monoclonal Antibody Charge Distribution and Monosaccharide Content"],"prefix":"10.1002","volume":"18","author":[{"given":"Albert E.","family":"Schmelzer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William M.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,9,5]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"Amgen Inc. 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