Ineffective erythropoiesis with reduced red blood cell survival in serotonin-deficient mice

被引：48

作者：

Amireault, Pascal ^{[1
,2
]}

Hatia, Sarah ^{[1
,2
]}

Bayard, Elisa ^{[1
,2
]}

Bernex, Florence ^{[3
,4
]}

Collet, Corinne ^{[5
]}

Callebert, Jacques ^{[5
]}

Launay, Jean-Marie ^{[5
]}

Hermine, Olivier ^{[1
]}

Schneider, Elke ^{[1
]}

Mallet, Jacques ^{[2
]}

Dy, Michel ^{[1
]}

Cote, Francine ^{[1
,2
]}

机构：

[1] Univ Paris 05, Hop Necker, CNRS, Fac Med,Unite Mixte Rech 8147, F-75743 Paris 15, France

[2] Univ Paris 06, Biotechnol & Biotherapy Lab,CNRS,UPMC, INSERM,Ctr Rech,Hop Pitie Salpetriere,Unite Mixte, Inst Cerveau & Moelle Epiniere,Unite Mixte Rech 7, F-75013 Paris, France

[3] Ecole Natl Vet Alfort, Unite Embryol Histol & Anat Pathol, F-94704 Maisons Alfort, France

[4] Ecole Natl Vet Alfort, Inst Natl Rech Agron, Unite Mixte Rech 955, F-94704 Maisons Alfort, France

[5] Hop Lariboisiere, AP HP, Serv Biochim, F-75010 Paris, France

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 32期

关键词：

HEMOLYTIC-ANEMIA; RECEPTOR; GENE; PROLIFERATION; DISRUPTION; MOUSE; PHOSPHATIDYLSERINE; DIFFERENTIATION; ERYTHROBLASTS; MORPHOGENESIS;

D O I：

10.1073/pnas.1103964108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Serotonin (5-HT) has long been recognized as a neurotransmitter in the central nervous system, where it modulates a variety of behavioral functions. Availability of 5-HT depends on the expression of the enzyme tryptophan hydroxylase (TPH), and the recent discovery of a dual system for 5-HT synthesis in the brain (TPH2) and periphery (TPH1) has renewed interest in studying the potential functions played by 5-HT in nonnervous tissues. Moreover, characterization of the TPH1 knockout mouse model (TPH1(-/-)) led to the identification of unsuspected roles for peripheral 5-HT, revealing the importance of this monoamine in regulating key physiological functions outside the brain. Here, we present in vivo data showing that mice deficient in peripheral 5-HT display morphological and cellular features of ineffective erythropoiesis. The central event occurs in the bone marrow where the absence of 5-HT hampers progression of erythroid precursors expressing 5-HT(2A) and 5-HT(2B) receptors toward terminal differentiation. In addition, red blood cells from 5-HT-deficient mice are more sensitive to macrophage phagocytosis and have a shortened in vivo half-life. The combination of these two defects causes TPH1(-/-) animals to develop a phenotype of macrocytic anemia. Direct evidence for a 5-HT effect on erythroid precursors is provided by supplementation of the culture medium with 5-HT that increases the proliferative capacity of both 5-HT-deficient and normal cells. Our thorough analysis of TPH1(-/-) mice provides a unique model of morphological and functional aberrations of erythropoiesis and identifies 5-HT as a key factor for red blood cell production and survival.

引用

页码：13141 / 13146

页数：6

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