Lymphocyte Ecto-5′-Nucleotidase Deficiency in Agammaglobulinemia

Edwards, N. Lawrence; Magilavy, DB; Cassidy, JT; Fox, I. H.

doi:10.1126/science.27864

Cited by 135 publications

(41 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The acquisition of greater plasma membrane 5'-nucleotidase activity may be one of many T-lymphocyte surface modifications occurring during T-cell differentiation (25). Inhibition of 5'-nucleotidase activity by adenosipea,3-methylene diphdsphonate is specific for 5'-nucleotidase but does not affect nonspecific phosphatase (2,16). Our observations indicate that the activity measured in peripheral mononuclear cells, th'mocytes, and B lymphoblasts is specific 5'-nucleotidase.…”

Section: Discussionmentioning

confidence: 55%

“…Lymphocyte 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) may have an important role in the regulation of the human immune system. Decreased activity of this purine catabolic enzyme has been observed in patients with primary immunoglobulin deficiency (1)(2)(3)(4). However, it remains unclear whether an etiological relationship exists between the immune dysfunction and this enzyme deficiency.…”

mentioning

confidence: 99%

“…To assess whether the AMP dephosphorylating activity measured by our enzyme assay on the lymphocyte surface is specific for 5'-nucleotidase or is a nonspecific phosphatase, inhibition of dephosphorylating activity by 25 (1)(2)(3)(4). Because abnormal T lymphocyte subpopulations may underlie the pathogenesis of the immune deficiency in these diseases (17,18), we compared the 5'-nucleotidase activity in peripheral E-rosette forming lymphocytes from nine normal subjects and five patients with congenital agammaglobulinemia (Table 3).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Distribution of 5'-nucleotidase in human lymphoid tissues.

Edwards¹,

Gelfand²,

Burk³

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Low activity of 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) in T lymphoblasts may explain the marked sensitivity of this cell to deoxynucleotide accumulation when compared to B Iymphoblasts. The relevance of such observations with cultured cells to the normal immune system requires the demonstration of similar differences in the 5'-nucleotidase activity of normal human lymphocyte subpopulations. Sheep erythrocyte (E) rosette-forming cells from normal thymus, tonsi , and peripheral mononuclear cells have 5'-nucleotidase activities of 1.7, 11.3, and 21.2 nmol/hr per 106 cells. Non-E-rosette forming cells from the peripheral blood or tonsil have 5'-nucleotidase activity comparable to the higher levels found in the peripheral E-RFC. Increased levels of5'-nucleotidase activity may be a marker for post-thymic T Iymphocytes.T lymphoblasts have 5'-nucleotidase activity similar to values demonstrated for E-RFC in thymus, whereas cultured B lymphoblasts have 5'-nucleotidase activity 15 times greater than that of T lymphoblasts. On the basis of these observations, the 5'-nucleotidase deficiency in congenital agammaglobulinemia has been reevaluated. In these patients the data indicate that peripheral E-rosette forming cells have the enzyme deficiency, demonstrating an abnormality of T lymphocytes in this disorder of immunoglobulin production. Lymphocyte 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) may have an important role in the regulation of the human immune system. Decreased activity of this purine catabolic enzyme has been observed in patients with primary immunoglobulin deficiency (1-4). However, it remains unclear whether an etiological relationship exists between the immune dysfunction and this enzyme deficiency.A marked difference in 5'-nucleotidase activity has been proposed as the molecular basis for the differential susceptibility of B and T lymphoblast lines to the toxicity related to deoxynucleoside accumulation (5-7). T lymphoblasts are killed by deoxyadenosine or deoxyguanosine, rapidly accumulate dATP or dGTP, and have very low levels of 5'-nucleotidase (5-9). In contrast, B lymphoblasts grow normally in deoxyadenosine or deoxyguanosine, accumulate only small quantities of deoxynucleoside triphosphates, and have higher 5'-nucleotidase levels than T lymphoblasts (5-9 and four T lymphoblast lines (CEM, Jurkat, MSB-2, and MOLT-3) were maintained and characterized as described (10).Peripheral lymphocytes were obtained, separated into Erosette forming cells and non-E-rosette forming cells, and characterized by described methods (11)(12)(13). Lymphoid organs were obtained from children with no known immune dysfunction, and cells were separated from these tissues within 1 hr of surgery by using described methods (14)

show abstract

Section: Discussionmentioning

confidence: 55%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Distribution of 5'-nucleotidase in human lymphoid tissues.

Edwards¹,

Gelfand²,

Burk³

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…This enzyme which occurs in both T and B lymphocytes is a marker for the maturation of these cells (2)(3)(4). Because NT is reduced in a number of congenital and acquired immunodeficiency disorders its measurement is now clinically desirable (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

A semi‐automated method for 5′‐ectonucleotidase measurement in lymphocytes

Chalmers

Hare

1990

Immunology & Cell Biology

View full text Add to dashboard Cite

Summary We describe a simple, non-radioactive, semi-automated method for measuring lymphocyte ccto-5'-nucleotidase activity in isolated cell homogenates. The method which uses inosine 5'-monophosphate(IMP)asa subslrate was optimized and requires a total of 4x 10*' lympbocytes. The reference range obtained (38 7-180 0 nmol/h per mg protein; .v= 106-6) agrees with other isotopic methods which use ''*C-IMP. The simplicity, sensitivity (lower limit 10, upper limit 400 nmol/h per mL) and precision (at 114 nmol/h per mL, interday4-2%s.d.,M = 20; intraday 5-8%, n * 10) makes this method suitable for routine eliniea! laboratory use.

show abstract

“…In both cases, the patients' loss of immune function can be directly attributed to alterations in purine ribo-and/or deoxyribonucleoside metabolism (8)(9)(10)(11)(12)(13)(14)(15). A deficiency of a third enzyme in the purine catabolic pathway, ecto-5'-nucleotidase (ecto-5'-NT), which is located on the external surface of the plasma membrane, has been reported in the lymphocytes of all patients with congenital agammaglobulinemia (CAG) (16,17) and the majority of patients with common variable immunodeficiency (CVI, or adult onset hypogammaglobulinemia) (18). Unlike deficiencies of ADA and PNP, the molecular and/or cellular basis of ecto-5'-NT deficiency is not well understood.…”

mentioning

confidence: 99%