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PubMed1991

Relationship of liver and skeletal muscle IGF-1 mRNA to plasma GH profile, production of IGF-1 by liver, plasma IGF-1 concentrations, and growth rates of cattle.

Growth hormone (GH), insulin-like growth factor-1 (IGF-1), and thyroid hormone (T3 and T4) concentrations in blood plasma of 18 crossbred cattle (six bulls, six steers, and six heifers) were measured over an 8-hr period. One week later at slaughter, IGF-1 production by liver slices and IGF-1 mRNA concentrations in skeletal muscle and liver were measured. Bulls had higher (P less than 0.05) mean plasma GH and GH peak amplitudes (P less than 0.01) than heifers, and values for steers were intermediate between bulls and heifers. Baseline GH concentrations and number of GH peaks were not significantly different for the three groups. Bulls had 1.6-fold (P less than 0.01) and 3.0-fold (P less than 0.01) greater liver IGF-1 mRNA concentrations than steers or heifers, respectively, whereas the steers had 1.8-fold (P less than 0.05) greater IGF-1 mRNA in liver than heifers. Production of IGF-1 by liver slices was greater (P less than 0.05) in bulls than steers or heifers. Bulls had 1.3-fold greater plasma IGF-1 than steers (P less than 0.01), whereas steers had 1.8-fold greater plasma IGF-1 than heifers (P less than 0.01). There were no significant differences in concentrations of skeletal muscle IGF-1 mRNA between the three groups of animals. Liver IGF-1 mRNA, liver IGF-1 production, and plasma IGF-1 were all significantly correlated with gain and mean GH peak amplitude, but not with GH baseline, GH peak frequency, or concentrations of T3 and T4. Concentrations if IGF-1 mRNA in skeletal muscle were not correlated to gain or any parameter of the GH profile. Plasma concentrations of T3 were significantly (P less than 0.05) negatively correlated to plasma GH baseline concentrations. Muscle IGF-1 mRNA concentration was negatively related to plasma T4 and T3. The results of this study suggest that the cascade of events starting with secretion of GH from the pituitary, expression of liver IGF-1 mRNA, and secretion of IGF-1 by the liver are important phenomena for growth of cattle.

Animals↗
PubMed1999

Association of plasma IgM with body size, histopathologic changes, and plasma chemistries in adult Pacific herring Clupea pallasi.

Pacific herring Clupea pallasi immunoglobulin is an IgM-like molecule comprised of heavy and light chains with molecular weights of 79 and 25 to 27 kD, respectively. Purified immunoglobulin was used to generate highly specific polyclonal antibodies for development of a sandwich ELISA. The ELISA was used to quantify total plasma IgM in 602 Pacific herring captured in Prince William Sound and Sitka Sound, Alaska, USA. Plasma IgM concentrations ranged from 0.13 to 5.32 mg ml-1. Using multiple stepwise regression analysis, plasma IgM was highly correlated (p < or = 0.01) with body length, Ichthyophonus hoferi infection, plasma albumin, plasma cholesterol, liver macrophage aggregates, and focal skin reddening. I. hoferi was the only organism significantly associated with plasma IgM. Gender, site, and season (spring vs fall) did not contribute to significant differences in plasma IgM. This study contributes to the understanding of the interaction of body size, plasma chemistries, and pathological changes upon circulating immunoglobulins in fish.

Alaska↗
PubMed1991

Plasma and yolk cholesterol levels in Japanese quail divergently selected for plasma cholesterol response to adrenocorticotropin.

Studies were conducted to determine the effect of divergent selection for plasma cholesterol response to adrenocorticotropin (ACTH) on the levels and relationships between plasma and yolk cholesterol in Japanese quail. Cholesterol data were obtained in Generation 25, following seven generations of relaxed selection, from birds maintained under a normal environment with no exposure to exogenous ACTH. Levels of plasma and yolk cholesterol were determined at 22 and 28 wk. Plasma cholesterol levels of quail in the low cholesterol line were significantly (P less than .01) lower than levels in the high line at both ages (224 versus 383 and 209 versus 326 mg/100 mL, respectively). In contrast, yolk cholesterol levels were significantly (P less than .01) higher in the low line than in the high line (24.1 versus 21.5 and 21.1 versus 16.9 mg cholesterol/g yolk at 22 and 28 wk, respectively). A significant line by sex interaction was present at both ages for plasma cholesterol with females having higher cholesterol values than males in the low line and males having higher values than females in the high line. A negative relationship was observed between changes in plasma and yolk cholesterol in the selected lines. Greater deposition of cholesterol in the yolk of the line with lower plasma cholesterol indicates that excretion rate may play a role in explaining genetic differences in plasma cholesterol.

Adrenocorticotropic Hormone↗
PubMed1976

Fitzgerald factor (high molecular weight kininogen) clotting activity in human plasma in health and disease in various animal plasmas.

Fitzgerald factor (high molecular weight kininogen) is an agent in normal human plasma that corrects the impaired in vitro surface-mediated plasma reactions of blood coagulation, fibrinolysis, and kinin generation observed in Fitzgerald trait plasma. To assess the possible pathophysiologic role of Fitzgerald factor, its titer was measured by a functional clot-promoting assay. Mean +/- SD in 42 normal adults was 0.99+/-0.25 units/ml, one unit being the activity in 1 ml of normal pooled plasma. No difference in titer was noted between normal men and women, during pregnancy, or after physical exercise. Fitzgerald factor activity was significantly reduced in the plasmas of eight patients with advanced hepatic cirrhosis (0.40+/-0.09 units/ml) and of ten patients with disseminated intravascular coagulation (0.60+/-0.30 units/ml), but was normal in plasmas of patients with other congenital clotting factor deficiencies, nephrotic syndrome, rheumatoid arthritis, systemic lupus erythematosus, or sarcoidosis, or under treatment with warfarin. The plasmas of 21 mammalian species tested appeared to contain Fitzgerald factor activity, but those of two avian, two repitilian, and one amphibian species did not correct the coagulant defect in Fitzgerald trait plasmas.

Adult↗
PubMed1975

Human plasma R-type vitamin B12-binding proteins. II. The role of transcobalamin I, transcobalamin III, and the normal granulocyte vitamin B12-binding protein in the plasma transport of vitamin B12.

The normal human granulocyte vitamin B12-binding protein, transcobalamin I, and transcobalamin III, have been labeled with 125I-labeled N-succinimidyl 3-(4-hydroxyphenyl)propionate and utilized for plasma clearance studies performed with rabbits. Both moieties of 125I-labeled granulocyte vitamin B12-binding protein-[57Co]vitamin B12 were cleared rapidly from the plasma (is less than 90% by 5 min) by the liver. After 30 min, the bulk of the 125I reappeared in the plasma in small molecular weight (less than 1000) form and was rapidly excreted in the urine. After 60 min the bulk of the [57Co]vitamin B12 reappeared in the plasma bound to rabbit transcobalamin II and was subsequently taken up by a variety of tissues. Approximately 15% of the 125I-labeled granulocyte vitamin B12-binding protein-[57Co-a1vitamin B12 was excreted intact into the bile during the period from 10 to 80 min after injection. The hepatic uptake of the protein-vitamin B12 complex was blocked by the prior injection of desialyzed fetuin but not by native fetuin. Similar results were obtained with 125I-labeled transcobalamin III-[57Co]vitamin B12. Approximately 90% of both moieties of 125I-labeled transcobalamin I-[57Co]vitamin B12 had prolonged plasma survivals similar to that of 125I-labeled bovine serum albumin. After treatment with neuraminadase, both moieties of the 125I-labeled transcobalamin I-[57Co]vitamin B12 complex were cleared rapidly from the plasma by the liver in a manner that was indistinguishable from that observed in the case of untreated granulocyte vitamin B12-binding protein and transcobalamin III. These observations indicate that desialyzed transcobalamin I and the native forms of the granulocyte vitamin B12-binding protein and transcobalamin III are cleared from plasma by the mechanism elucidated by Ashwell and Morell (Ashwell, G., and Morell A. G. (1974) Adv. Enzymol. 41, 99-128) that is capable of clearing a wide variety of asialoglycoproteins. These observations have implications concerning the function of the human R-type vitamin B12-binding proteins, the nature of the enterohepatic circulation of vitamin B12, the biological significance of the mechanism described by Ashwell and Morell, and the etiology of the increased plasma concentration of human R-type protein that occurs frequently in chronic myelogenous leukemia and occasionally in hepatocellular carcinoma and other solid tumors.

Animals↗
PubMed1992

Vampire bat salivary plasminogen activator promotes robust lysis of plasma clots in a plasma milieu without causing fluid phase plasminogen activation.

Vampire bat salivary plasminogen activator (BatPA), human tissue-type plasminogen activator (tPA) or streptokinase (SK) were incubated in human citrated plasma containing a plasma clot that was radiolabelled with iodine-125 fibrin(ogen). Complete clot dissolution by BatPA (30 nM) was associated with slight activation of "fluid phase" plasminogen; the plasma levels of functional fibrinogen and alpha 2-antiplasmin decreased by only 8 and 19%, respectively. Addition of SK (3,600 IU/ml) to the clot-containing plasma caused complete clot lysis and massive activation of the "fluid phase" plasminogen, leading to greater than 60 and 96% decreases of the functional levels of fibrinogen and alpha 2-antiplasmin, respectively. Incubation of tPA (30 nM) in clot-containing plasma caused complete clot lysis as well as substantial activation of "fluid phase" plasminogen; the plasma levels of functional fibrinogen and alpha 2-antiplasmin decreased by 45 and 79%, respectively. The profound degradation of fibrinogen in the SK and tPA but not BatPA-containing samples was confirmed by immunoblot analysis. Additional experiments showed that the presence of soluble clot lysate in plasma containing tPA enhanced the extent of fibrinogen degradation from 25% to greater than 60%; the addition of soluble clot lysate to the plasma containing BatPA did not prompt further fibrinogen degradation. Finally, studies using exogenous alpha 2-antiplasmin suggested that plasmin generated via tPA-mediated activation of "fluid phase" plasminogen does not play an important role in clot dissolution.

Animals↗
PubMed2006

[Changes of maternal plasma and umbilical cord plasma inhibin and epidermal growth factor in patients with hypertensive disorder complicating pregnancy].

OBJECTIVE: To study the levels of inhibin (INH) and epidermal growth factor (EGF) in maternal plasma and umbilical cord plasma of patients with hypertensive disorder complicating pregnancy, and to explore their influence on the disease and fetal growth. METHODS: Enzyme linked immunosorbent assay (ELISA) was used to detect maternal and umbilical cord plasma INH and EGF levels in 65 patients with hypertensive disorder complicating pregnancy (test groups) and 21 normal pregnant women (control group). RESULTS: Plasma level of INH in test groups (499 +/- 52) ng/L was significantly higher than that (421 +/- 36) ng/L in control group (P < 0.01); however, the umbilical cord plasma level of INH had no significant difference (P > 0.05). Plasma level of EGF in test groups (408 +/- 60) ng/L was significantly lower than that (463 +/- 87) ng/L in control group (P < 0.05), also there was significant difference in umbilical cord plasma level of two groups (232 +/- 99) ng/L vs (380 +/- 97) ng/L (P < 0.01). The level of EGF in umbilical cord blood was positively correlated with newborn's body weight and placental weight. CONCLUSIONS: Plasma levels of INH and EGF in pregnancy women are related with hypertensive disorder complicating pregnancy. EGF level of umbilical cord blood affects the growth of fetus and placenta.

Adult↗
PubMed1975

[Plasma renin activity and plasma aldosterone during anaesthesia and operative stress and beta-adrenergic blockade (author's transl)].

In 21 patients undergoing ear operations associated with minimal bleeding plasma renin activity and plasma aldosterone concentration were studied before and during surgical procedure, and in the postoperative state. Studies were performed in two groups, one without (n=9) and one with beta-adrenergic blockade by Practolol (n=12). Plasma renin activity increased significantly during halothane anaesthesia alone whereas the surgical manipulations did not further influence mean values significantly. Thus, it seems to be established that anaesthesia per se influences renin secretion. On the other hand Practolol does not show an inhibiting effect. The plasma renin increase following anaesthesia is due to the hemodynamic including renal hemodynamic, changes as well as to activation of the sympatho-adrenal system. Changes in plasma aldosterone are variable. For the greater part of patients with beta-adrenergic blockade an increase during the operative procedure was found. However, in some patients especially in the control group, plasma aldosterone was unchanged or decreased in spite of increasing renin values. Significantly lower plasma potassium concentration in these cases seems to indicate the important contributing role of potassium for the short-term regulation of aldosterone secretion. Plasma sodium concentration remained unchanged for the periods studied.

Adolescent↗
PubMed1985

Distribution of plasma kallikrein between C-1 inactivator and alpha 2-macroglobulin in plasma utilizing a new assay for alpha 2-macroglobulin-kallikrein complexes.

We have previously described an enzyme-linked immunosorbent assay for the quantification of C-1 inactivator-kallikrein complexes in plasma (Lewin, M. F., Kaplan, A. P., and Harpel, P. C. (1983) J. Biol. Chem. 258, 6415-6421). We have now developed an immunoimmobilization-enzyme assay for alpha 2-macroglobulin-kallikrein complexes. In this assay these complexes are removed from plasma by immunoabsorption with the IgG fraction of rabbit anti-alpha 2-macroglobulin antiserum coupled to an agarose gel. The immobilized alpha 2-macroglobulin-kallikrein complex hydrolyzes the fluorogenic substrate D-Ser-Pro-Phe-Arg-7-amino-4-trifluoromethyl coumarin, and this activity is proportional to the concentration of complexes in the plasma. Using these assays we have studied the distribution of plasma kallikrein between its inhibitors under several different experimental conditions. When kallikrein is added to plasma, about 57% binds to C-1 inactivator and 43% to alpha 2-macroglobulin. When prekallikrein is activated endogenously in plasma by the addition of kaolin or Hageman factor fragment, approximately 84% of kallikrein is now bound to C-1 inactivator and 16% to alpha 2-macroglobulin. Temperature dramatically affects the distribution of kallikrein. The binding of kallikrein to alpha 2-macroglobulin in plasma is inversely related to temperature, whereas the binding to C-1 inactivator is directly related: 85% of the kallikrein is bound to alpha 2-macroglobulin at 4 degrees C, whereas at 37 degrees C, only 33% is bound. The total amount of kallikrein bound to the two inhibitors is similar at each temperature. These studies thus provide new insight concerning kallikrein formation and regulation in plasma.

Complement C1 Inactivator Proteins↗
PubMed1987

Plasma erythropoietin assay by a fetal mouse liver cell culture method with special reference to effective elimination of erythroid colony inhibitor(s) in plasma.

Methods for the elimination of an inhibitor(s) of erythroid colony formation from plasma were examined in an attempt to measure genuine plasma erythropoietin (Epo) activities with an erythroid colony-forming assay using fetal mouse liver cells. Acid-boiling-chloroform (ABC) treatment was concluded to be the best method because the plasma thus treated stimulated colony formation most and contained the least protein. The dose-response curve for the plasma was parallel to that for the standard Epo preparation. The "erythroid colony-stimulating activity" in the plasma was completely additive to that in the standard Epo, and appeared to be a relatively heat-stable and acid protein with an isoelectric point lower than 5.0. These results suggest that the activity in the plasma is identical to that in the standard Epo. Stability of the plasma Epo activity was dependent on storage temperature and enhanced by adding 1% bovine serum albumin (BSA). Average Epo titers for normal adult, full-term cord, and murine plasmas, all ABC-treated and with 1% BSA added, were 192.4, 184.5, and 150.6 mU/ml, respectively. These values were much higher than those measured by the in vivo standard polycythemic mouse assay.

Animals↗
PubMed1993

Detection of interleukin-8 (IL-8) in seminal plasma and elevated IL-8 in seminal plasma of infertile patients with leukospermia.

OBJECTIVE: To determine if interleukin-8 (IL-8) is a normal constituent of seminal plasma and if leukospermia is a factor determining its elevation. DESIGN: Seminal plasma from 58 men obtained by masturbation was examined for the presence of IL-8 using an IL-8 specific sandwich ELISA. Semen samples were obtained from 34 infertile men without leukospermia, 10 infertile men with leukospermia, and 14 proven fertile men. The correlation of amount of IL-8 in seminal plasma with some spermiogram parameters and the amount of polymorphonuclear (PMN) elastase was statistically evaluated. RESULTS: Immunoreactive IL-8 was observed in the seminal plasma of all 58 subjects. The IL-8 titer in seminal plasma of patients with leukospermia (6.16 +/- 0.82 micrograms/L) was significantly higher than that in seminal plasma of patients without leukospermia (2.35 +/- 0.34 micrograms/L) and fertile men (1.64 +/- 0.29 micrograms/L). There was a high degree of correlation between PMN elastase and IL-8 levels in seminal plasma. CONCLUSIONS: These findings demonstrate IL-8 to be in seminal plasma and elevated IL-8 levels in infertile patients with leukospermia.

Humans↗
PubMed1999

Pentastarch as partial replacement fluid for therapeutic plasma exchange: effect on plasma proteins, adverse events during treatment, and serum ionized calcium.

We compared the safety, effect on plasma proteins, and contribution to hypocalcemic toxicity of 10% pentastarch vs. 5% albumin in plasma exchange. Thirty-two neurology patients underwent 161 plasma exchange procedures. Subjects were randomized to receive either 10% pentastarch (n = 17) or 5% albumin (n = 15) as the first (1/2) of colloid replacement. The second (1/2) of colloid replacement was 5% albumin in all cases. NaCl (plus small amounts of ACD-A) accounted for (1/4) of the total return fluid. Mean total exchange volume was 3,842.6 +/- 450 ml. Hemoglobin, platelet count, coagulation parameters, and plasma fibrinogen were similar between the two groups at the outset of plasma exchange and at the time of the last (4th or 5th) procedure of the series. Immunoglobulin levels were equivalent at the outset and were reduced by plasma exchange to the same extent in the two groups. Serum albumin concentration fell significantly faster in the group receiving pentastarch. On the other hand, serum calcium, corrected for the albumin concentration, fell significantly further in the control group than in the group receiving pentastarch. Mean serum ionized calcium fell approximately 25 % in procedures using only albumin but only approximately 16% when pentastarch was used (P < 0.0001). This was reflected in the occurrence of hypocalcemic toxicity in 33.3% of procedures performed using only albumin but in only 8.1% of those using pentastarch (P = 0.0002). Pentastarch may be suitable for partial colloid replacement in plasma exchange and would have saved our hospital $127,050 to $434,280 in 1998 if used in all procedures.

Adult↗
PubMed1996

Plasma exchange with solvent/detergent-treated plasma of resistant thrombotic thrombocytopenic purpura.

A patient with unremitting thrombotic thrombocytopenic purpura (TTP), with circulating von Willebrand factor (VWF) multimers of unusually high molecular weight, and refractory to standard plasma exchange therapy, was treated with solvent detergent (S/D) plasma. The patient achieved a sustained clinical and haematological remission, with normal VWF multimeric profile. Spontaneous remission of this patient's condition could not be excluded but would appear unlikely. S/D plasma was efficacious and potentially safe for repeated large-volume plasma exchange with respect to viral safety and reduction of anaphylactoid reactions. We have assayed coagulation factors and physiological inhibitors of haemostasis in S/D plasma, which were comparable to normal plasma except in the distribution of VWF multimers. The use of S/D plasma, previously reported in paediatric chronic relapsing TTP, should be assessed in further cases of adult TTP in the context of a clinical trial.

Adult↗
PubMed2006

Time course of organ dysfunction in thrombotic microangiopathy patients receiving either plasma perfusion or plasma exchange.

INTRODUCTION: Few studies have investigated adults with thrombotic microangiopathy (TMA) requiring intensive care unit (ICU) admission, and the treatment remains controversial. OBJECTIVE: To describe causes, outcomes, prognostic factors, and daily organ-failure score changes in adults with TMA requiring ICU admission. DESIGN: A 3-yr single-center cohort study. PATIENTS: The patients were 36 adults with TMA admitted to a teaching-hospital medical ICU between January 2000 and June 2003. RESULTS: Of the 36 patients, 22 received plasma infusion and 15 underwent plasma exchange. All patients had anemia and thrombocytopenia at ICU admission, and 13 had neurologic impairment. Median creatinine clearance was 55.2 mL/min (interquartile range, 28.8-75.4). No patient had congenital TMA. Causative factors included microbiologically documented infection in 14 patients, allogeneic transplantation in 7 patients, and concomitant or subsequent systemic disease in 7 patients; 6 patients were human immunodeficiency virus-positive, 5 had drug-induced TMA, 2 were pregnant, and 2 had cancer. In 10 patients, no causative factors were identified. Plasma exchange was associated with a statistically significant decrease in hospital mortality (0 vs. 7 deaths; p < .001). Moreover, daily organ-failure scores were significantly lower in the plasma-exchange group from day 3 to day 9. Patients in the plasma-exchange group received a larger volume of plasma. CONCLUSION: Plasma exchange may be associated with faster resolution of organ failure and with improved survival for patients with TMA requiring ICU admission.

Adult↗
PubMed2006

The application of Beckman Coulter VCS technology at a major cancer center, with emphasis on the detection of circulating immature plasma cells in plasma cell leukemia.

The St. Vincent's Comprehensive Cancer Center (SVCCC) has a large multiple myeloma program in downtown New York City. The laboratory at SVCCC is an integral part of the diagnosing and monitoring of its myeloma patients. Circulating plasma cells are not a common finding in multiple myeloma. Being able to detect plasma cells in peripheral blood is important because they are a prognostic indicator that correlates with disease progression. Furthermore, the peripheral blood plasma cell population can demonstrate morphologic variability. Immature plasma cells, both plasmablasts and proplasmacytes are associated with more aggressive disease and shortened survival. We encountered 3 multiple myeloma patients with circulating immature plasma cells that appeared as distinct populations on our hematology analyzer's automated white blood cell (WBC) differential. The immature plasma cells, given their unique cellular characteristics, appeared in a common place within the WBC differential scatterplot in each patient. In our laboratory, we have utilized this common graphic pattern to screen for immature plasma cells. This pattern has proven to be a useful tool in our large population of multiple myeloma patients. We have also used examination of the scatterplots in other hematologic malignancies such as chronic lymphocytic leukemia. Using this review policy, the laboratory has been able to achieve a smear review of 25% in our highly abnormal patient population.

Autoanalysis↗
PubMed1983

Use of plasma volume substitutes and plasma in developing countries.

Plasma and plasma substitutes are used in the treatment of various conditions such as haemorrhage and shock. This article examines the role of crystalloids, artificial colloids, human plasma, human albumin, and plasma protein fraction, in the treatment of such patients, with particular reference to peripheral health facilities in developing countries.It is concluded that 0.9% saline, together with 5-6% dextrose, is of particular importance in this situation since it is easy to produce locally, is stable at high temperatures, and has a low cost/benefit ratio. The second priority is to ensure the availability of a limited quantity of one or more colloid plasma substitutes. In the field of plasma, fresh frozen or fresh liquid plasma is most useful for the treatment of various haemostatic derangements and follow-up treatment of severe burns, since it contains the widest spectrum of therapeutically useful components and can be produced locally with an acceptable degree of difficulty.The treatment of severe diarrhoea with special alkaline electrolyte solutions and oral rehydration solutions is also outlined.

Burns↗
PubMed1987

Nomograms for the prediction of patient's plasma volume in plasma exchange therapy from height, weight, and hematocrit.

The knowledge of plasma volume (PV) is a basic requirement for the standardization of plasma exchange therapy. PV has to be determined by calculation, as the measurement of PV before every plasma exchange is too cost- and time consuming. A known correlation with measured values results from calculation of plasma volume by means of patient's height and weight. But the present equations are only reliable at normal hematocrit. For this reason we modified the Retzlaff-equations and compared the validity of plasma volume predictions, calculated by these and own equations, with plasma volume measured by the 51Cr-method in 59 patients with pathological hematocrit. The correlation coefficient was 0.82 for men and 0.81 for women (2 0.001) with the modified Retzlaff-equations. On the average the relative error was -1.5% for all and 2.8% for fat and thin men. No significant improvement of accuracy was achieved with other equations. Thus, plasma volume can accurately be calculated from height, weight, and hematocrit with our modified Retzlaff-equations in patients with pathological hematocrit, even if they are very fat or thin. Nomograms for men and women were constructed in order to facilitate the calculation.

Blood Volume Determination↗
PubMed1993

T cell-dependent differentiation of human B cells into IgM, IgG, IgA, or IgE plasma cells: high rate of antibody production by IgE plasma cells, but limited clonal expansion of IgE precursors.

The development of human functional Ig precursors into plasma cells expressing IgM, IgG, IgA, or IgE was compared. Purified human B cells were stimulated at limiting dilution with irradiated EL4 helper cells, IL-2, and IL-4. B cells proliferated exponentially until Day 8 of culture. Nondividing plasma cells of all isotypes were detectable in ELISPOT assays between Days 8 and 10 and secreted 1.8 +/- 0.7 ng antibody per cell within 24 hr. This indicates that plasma cells of all isotypes, including IgE, bear a comparable potential to secrete antibody. It further shows that Ig switching does not delay the development into IgE plasma cells, despite that switching from IgM to IgE in vitro required 6 days of IL-4 action. The proliferation and Ig production by B cells readily declined after Days 8 and 10, respectively, and could not be prolonged by restimulating B cells with fresh helper cells and lymphokines in secondary cultures. This indicates that B cells have developed into nondividing, high rate Ig-secreting plasma cells within 9 days, and that they do not differentiate any further under the applied conditions. In contrast to IgM, IgG, and IgA committed B cells, IgE switched cells did not undergo clonal expansion, since the numbers of functional IgE precursors corresponded to the maximal numbers of IgE-secreting plasma cells, whereas the numbers of IgM-, IgG-, or IgA-secreting cells exceeded the number of functional precursors 15-fold. The results demonstrate that human B cells of all isotypes, including IgE, have the potential to secrete antibody at a comparably high rate, and that the IL-4-induced switch process does not delay the differentiation into plasma cells.

Animals↗