In Southeast Asia, Miltenberger antigen subtype III (Mi.III; GP.Mur) is considered one of the most important red blood cell antigens in the field of transfusion medicine. Mi.III functions to promote erythrocyte band 3 expression and band 3-related HCO3− transport, with implications in blood CO2 metabolism. Could Mi.III affect physiologic CO2 respiration in its carriers? Here, we conducted a human trial to study the impacts of Mi.III expression in respiration. We recruited 188 healthy, adult subjects for blood typing, band 3 measurements, and respiratory tests before and after exercise. The 3-minute step exercise test forced the demand for CO2 dissipation to rise. We found that immediately following exercise, Mi.III + subjects exhaled CO2 at greater rates than Miltenberger-negative subjects. Respiration rates were also higher for Mi.III + subjects immediately after exercise. Blood gas tests further revealed distinct blood CO2 responses post-exercise between Mi.III and non-Mi.III. In contrast, from measurements of heart rates, blood O2 saturation and lactate, Mi.III phenotype was found to be independent of one’s aerobic and anaerobic capacities. Thus, Mi.III expression supported physiologic CO2 respiration. Conceivably, Mi.III + people may have advantages in performing physically enduring activities.
Erythroid RhD and RhCcEe were differentially expressed at the transcript levels, which could be related to their different degrees of interaction or sensitivity to RhAG. Further, the reduction or absence of glycophorin B in GYP.Mur erythroid cells affected transcript expressions of RhAG and RhCcEe. Thus, GPB and GP.Mur differentially influenced Rh/RhAG expressions prior to protein translation.
GP.Mur is a clinically important red blood cell (RBC) phenotype in Southeast Asia. The molecular entity of GP.Mur is glycophorin B-A-B hybrid protein that promotes band 3 expression and band 3–AQP1 interaction, and alters the organization of band 3 complexes with Rh/RhAG complexes. GP.Mur+ RBCs are more resistant to osmotic stress. To explore whether GP.Mur+ RBCs could be structurally more resilient, we compared deformability and osmotic fragility of fresh RBCs from 145 adults without major illness (47% GP.Mur). We also evaluated potential impacts of cellular and lipid factors on RBC deformability and osmotic resistivity. Contrary to our anticipation, these two physical properties were independent from each other based on multivariate regression analyses. GP.Mur+ RBCs were less deformable than non-GP.Mur RBCs. We also unexpectedly found 25% microcytosis in GP.Mur+ female subjects (10/40). Both microcytosis and membrane cholesterol reduced deformability, but the latter was only observed in non-GP.Mur and not GP.Mur+ normocytes. The osmotic fragility of erythrocytes was not affected by microcytosis; instead, larger mean corpuscular volume (MCV) increased the chances of hypotonic burst. From comparison with GP.Mur+ RBCs, higher band 3 expression strengthened the structure of RBC membrane and submembranous cytoskeletal networks and thereby reduced cell deformability; stronger band 3–AQP1 interaction additionally supported osmotic resistance. Thus, red cell deformability and osmotic resistivity involve distinct structural–functional roles of band 3.
GP.Mur, commonly known as Miltenberger subtype III, is a clinically‐important red blood cell (RBC) phenotype unique among Southeast Asians (SEA). On the GP.Mur+ erythrocyte membrane, glycophorin B‐A‐B hybrid protein is expressed, instead of glycophorin B (GPB). Different from GPB that does not have any known function, GP.Mur hybrid protein promotes expression of anion exchanger‐1 (AE1) on the RBC membrane and support AE1‐relevant physiological functions in GP.Mur+ carriers. In our previous human studies, we unexpectedly uncovered that GP.Mur+ carriers have slightly higher blood pressure (BP) than GP.Mur‐negative people. Since AE1 has been implicated a role in modulation of NO bioavailability and hemoglobin (Hb) is a major NO scavenger, we hypothesized that the slightly but significantly higher BP in GP.Mur carriers might be related to Hb‐mediated NO processing. Methods With the approval of hospital Institutional Review Board, healthy, non‐smoker subjects aged between 20 and 55 were recruited at Taitung MacKay Memorial Hospital (TT‐MMH). Besides general physical assessment, recruited subjects were tested for CBC and RBC phenotypes, including GP.Mur. Results 345 male and 515 female non‐smoker adults were recruited from Taitung County, Taiwan, and 22.1% of them bear GP.Mur blood type. For male and female cohorts, GP.Mur erythrocyte expression was significantly associated with slightly higher systolic BP (SBP) (122.2±12.9 mmHg [non‐GP.Mur male] versus 127.8±14.4 mmHg [GP.Mur male]; 115.0±13.0 mmHg [non‐GP.Mur female] versus 118.0±13.4 mmHg [GP.Mur female]). Hb levels were not affected by GP.Mur. Hb is known to be positively associated with SBP. We indeed found a Pearson correlation of 0.164 between Hb (g/dL) and SBP (mmHg) in non‐GP.Mur male subjects (*p~0.007). However, Hb‐SBP associations were not observed in our female cohorts with or without GP.Mur. Intriguingly, the Pearson correlation between Hb and SBP from the GP.Mur male group was doubled, compared to that from the GP.Mur‐negative male group (Pearson correlation: 0.299 [GP.Mur male] versus 0.164 [non‐GP.Mur male]). Conclusion From the differences in Hb‐SBP correlations in male, the effects of NO‐scavenging by Hb were likely more substantial in the presence of GP.Mur and/or higher AE1 expression. We did not observe any positive associations in our SEA female subjects, presumably due to menstrual cycle and that SEA women were generally more anemic.
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