Hereditary sideroblastic anemia and glucose-6-phosphate dehydrogenase deficiency in a negro family

Prasad, Ananda S.; Tranchida, Liborio; Konno, Edward T.; Berman, Laurence; Albert, S.; Sing, Charles F.; Brewer, George J.

doi:10.1172/jci105833

Cited by 32 publications

(6 citation statements)

References 32 publications

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“…Erythrocyte clearance has been studied for many years in the context of normal turnover, 1,2 enhanced clearance resulting from defects in erythrocyte metabolism or changes in membrane composition, [3][4][5] and in blood transfusion. 6 A large number of factors that may influence erythrocyte clearance have been proposed, ranging from autoantibody binding to band 3 after conformational changes resulting from aging (the "senescent cell antigen"), 7,8 to the expression of phosphatidylserine on the outer leaflet of the erythrocyte membrane.…”

Section: Introductionmentioning

confidence: 99%

CD47 functions as a molecular switch for erythrocyte phagocytosis

Burger

Hilarius-Stokman

Korte

et al. 2012

Blood

276

289

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CD47 on erythrocytes inhibits phagocytosis through interaction with the inhibitory immunoreceptor SIRP␣ expressed by macrophages. Thus, the CD47-SIRP␣ interaction constitutes a negative signal for erythrocyte phagocytosis. However, we report here that CD47 does not only function as a "do not eat me" signal for uptake but can also act as an "eat me" signal. In particular, a subset of old erythrocytes present in whole blood was shown to bind and to be phagocytosed via CD47-SIRP␣ interactions. Furthermore, we provide evidence that experimental aging of erythrocytes induces a conformational change in CD47 that switches the molecule from an inhibitory signal into an activating one. Preincubation of experimentally aged erythrocytes with human serum before the binding assay was required for this activation. We also demonstrate that aged erythrocytes have the capacity to bind the CD47-binding partner thrombospondin-1 (TSP-1) and that treatment of aged erythrocytes with a TSP-1-derived peptide enabled their phagocytosis by human red pulp macrophages. Finally, CD47 on erythrocytes that had been stored for prolonged time was shown to undergo a conformational change and bind TSP-1. These findings reveal a more complex role for CD47-SIRP␣ interactions in erythrocyte phagocytosis, with CD47 acting as a molecular switch for controlling erythrocyte phagocytosis. (Blood. 2012;119(23):5512-5521) IntroductionErythrocyte clearance has been studied for many years in the context of normal turnover, 1,2 enhanced clearance resulting from defects in erythrocyte metabolism or changes in membrane composition, [3][4][5] and in blood transfusion. 6 A large number of factors that may influence erythrocyte clearance have been proposed, ranging from autoantibody binding to band 3 after conformational changes resulting from aging (the "senescent cell antigen"), 7,8 to the expression of phosphatidylserine on the outer leaflet of the erythrocyte membrane. 9 In general, it is thought that erythrocytes are cleared after accumulating so-called "eat me" signals and are then phagocytosed by macrophages of the reticuloendothelial system, predominantly in the spleen and liver. 1,10,11 In contrast, one of the membrane proteins expressed by erythrocytes, CD47, has been shown to inhibit phagocytosis of erythrocytes by macrophages of the reticuloendothelial system. 12-16 CD47 exerts its inhibitory effect through binding to SIRP␣ on the macrophage, which induces inhibitory signaling by the immunoreceptor tyrosinebased inhibition motifs (ITIMs) residing in the cytoplasmic tail of SIRP␣. 17,18 On ligation of SIRP␣ by CD47, the SIRP␣ ITIMs recruit and activate tyrosine phosphatases SHP-1 and SHP-2, and this regulates, generally in a negative fashion, downstream signaling pathways and effector functions. The inhibitory effect of CD47 on erythrocyte clearance can be illustrated by transfusion of CD47-deficient erythrocytes into a wild-type recipient, which leads to rapid phagocytosis of the CD47-deficient erythrocytes by red pulp macrophages in the spleen. 12,19 ...

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Section: Introductionmentioning

confidence: 99%

CD47 functions as a molecular switch for erythrocyte phagocytosis

Burger

Hilarius-Stokman

Korte

et al. 2012

Blood

276

289

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“…Linkage studies in families with X linked hereditary sideroblastic anaemia have been uninformative for G6PD,27 uninformative for Xga, [27][28][29] '5 reported males with delayed onset (between 2 and 16 years) ataxia that progressed to loss of ambulation and included pes cavus, scoliosis, dysmetria, dysarthria, muscle wasting, hyperactive tendon reflexes, and Babinski responses, as well as impaired position and vibration sense in adults. While the neurological findings in the family reported by Shokeir6 were similar to those manifest by our patients, his patients had delayed onset of their cerebellar symptoms (between 6 and 23 years) and progressive deterioration until the age of 3() years.…”

mentioning

confidence: 99%

Hereditary sideroblastic anaemia and ataxia: an X linked recessive disorder.

Pagon¹,

Bird²,

Detter³

et al. 1985

Journal of Medical Genetics

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SUMMARY We report two families in which a non-progressive spinocerebellar syndrome and a sideroblastic anaemia are segregating together in an X linked recessive fashion. Four males in two generations of one family and a fifth male from an unrelated family had both conditions. Both the sideroblastic anaemia and the spinocerebellar syndrome differ from those which have previously been reported to be inherited in an X linked recessive manner. The association of these two clinically distinct disorders in two unrelated families suggests that they are either two closely linked loci which have undergone simultaneous mutation or pleiotropic effects of an altered allele at a single locus.All the heterozygous women had normal neurological examinations and normal haematocrits and red cell indices. Some had ring sideroblasts on bone marrow examination, a dimorphic peripheral blood smear, and raised serum free erythrocyte protoporphyrin, suggesting that a proportion of heterozygotes can be detected by appropriate haematological studies.We report two families in which a sideroblastic anaemia and spinocerebellar syndrome are segregating together in an X linked recessive fashion. Affected males have a moderate hypochromic, microcytic anaemia with ring sideroblasts on bone marrow examination. Although similar to the previously described X linked hereditary sideroblastic anaemia, this disorder is characterised by raised, rather than normal or low, free erythrocyte protoporphyrin levels and by a lack of excessive parenchymal iron storage in adulthood. The spinocerebellar disorder is different from the other reported X linked ataxias. It is characterised by a non-progressive ataxia and incoordination, as well as long motor tract signs in the younger affected boys. Intelligence is normal. Some heterozygous females have ring sideroblasts on bone marrow examination, a dimorphic peripheral blood smear, and raised serum free erythrocyte protoporphyrin. The proband (patient IV.5) was a 51/2 year old white Received for publication 15 February 1984. Accepted for publication 2 August 1984. male born at term, weighing 3-1 kg. At one year of age he had developmental delays because of truncal ataxia, dysmetria, and tremulousness. At 21/2 years of age, when admitted to hospital for an unrelated illness, he was found to be anaemic (table 1). Peripheral blood smear showed microcytic, hypochromic red cells with anisocytosis and cigarshaped cells. He had no hepatosplenomegaly. Bone General physical examination was normal including height (83-0 cm) and OFC (49 cm). He had marked ataxia while sitting which usually required him to assume a tripod position, marked dysmetria, pathologically brisk deep tendon reflexes in his lower extremities, and a left extensor plantar response. Muscle tone was normal. He had no nystagmus or strabismus.Three males (IV.4, IV.6, and IV.7) who were normal neurologically had normal haematocrits, haemoglobin levels, red cell indices, and peripheral smears.The obligate heterozygote women (11. 1, 111.2, III.6, and II1.7...

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“…Erythrocyte clearance has been studied for many years in the context of normal turnover [1,2], enhanced clearance due to defects in erythrocyte metabolism or changes in membrane composition [3][4][5], and in blood transfusion [6]. Traditionally, erythrocyte phagocytosis has been proposed to be the result of the accumulation of 'eat me' signals on the membrane of Intriguingly, evidence exists in the literature that the CD47-SIRP interaction, besides its inhibitory function on phagocytosis, can also promote cell-cell interactions [23] and even mediate phagocytosis of apoptotic cells [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

CD47 in Erythrocyte Ageing and Clearance the Dutch Point of View

Burger

Korte²,

Berg³

et al. 2012

Transfus Med Hemother

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Recently, an important role for CD47, a well-known ‘don’t eat me’ signal, in the clearance of aged erythrocytes was revealed. Experimental data support the conversion of CD47 from a ‘don’t eat me’ to an ‘eat me’ signal through a conformational change in CD47. Intriguingly, erythrocyte phagocytosis after this switch seems to be mediated by the same receptor that normally signals inhibition of phagocytosis, SIRPα. In this review, the possible molecular mechanisms leading to this conformational change in CD47 as well as the possible signal transduction events leading to phagocytosis after this switch are discussed. Lastly, the consequences of this newly identified mode of erythrocyte phagocytosis for the clearance of aged erythrocytes during normal turnover and after erythrocyte transfusion are addressed.

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Hereditary sideroblastic anemia and glucose-6-phosphate dehydrogenase deficiency in a negro family

Cited by 32 publications

References 32 publications

CD47 functions as a molecular switch for erythrocyte phagocytosis

CD47 functions as a molecular switch for erythrocyte phagocytosis

Hereditary sideroblastic anaemia and ataxia: an X linked recessive disorder.

CD47 in Erythrocyte Ageing and Clearance the Dutch Point of View

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Hereditary sideroblastic anemia and glucose-6-phosphate dehydrogenase deficiency in a negro family

Cited by 32 publications

References 32 publications

CD47 functions as a molecular switch for erythrocyte phagocytosis

CD47 functions as a molecular switch for erythrocyte phagocytosis

Hereditary sideroblastic anaemia and ataxia: an X linked recessive disorder.

CD47 in Erythrocyte Ageing and Clearance  the Dutch Point of View

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CD47 in Erythrocyte Ageing and Clearance the Dutch Point of View