Modulation of the expression and activity of cyclooxygenases in normal and accelerated erythropoiesis.
OBJECTIVE
The present study was aimed at characterizing the expression and activity of cyclooxygenase (COX) isoenzymes in erythropoiesis.


METHODS
The expression and activity of cyclooxygenase (COX) and prostaglandin (PG) synthases were investigated in: 1) erythroblasts developed in culture from human CD34(+) hematopoietic progenitors, 2) erythroblasts in bone marrow specimens, and 3) peripheral erythrocytes isolated from healthy donors and from patients with a high regeneration rate of erythrocytes.


RESULTS
While COX-1 protein was observed at each stage of erythroblast development, COX-2 protein was induced at later stages through a p38/MAPK-dependent pathway. Both COX isoforms were also observed in mature erythroblasts of the bone marrow. Erythroblasts developed in culture synthesized significantly more PGE(2) than TXB(2) and indomethacin delayed erythroid maturation. COX-1 and COX-2 were also observed in erythrocytes by immunostainings, although COX expression was confined to a fraction of circulating erythrocytes. Peripheral erythrocytes synthesized low but detectable amounts of PGE(2) and TXB(2). Similarly to erythroblast progenitors, PGE(2) was the prevalent prostanoid released by erythrocytes. This biosynthetic capacity was significantly increased in erythrocytes from patients with accelerated erythropoiesis as compared to controls.


CONCLUSIONS
Both COX isoforms are present and enzymatically active during human erythropoiesis, although with different kinetics, and COX-derived prostanoids may play a role in erythroid maturation. Furthermore, peripheral erythrocytes retain in part the capacity of expressing COX and synthesizing prostanoids, which may contribute to the hemostatic/thrombotic response to vascular injury in different diseases, including congenital hemolytic disorders.
Rocca
Bianca
B
Departments of Internal Medicine, Catholic University School of Medicine, 00168 Rome, Italy. b.rocca@tiscali.it
Secchiero
Paola
P
Celeghini
Claudio
C
Ranelletti
Franco O
FO
Ciabattoni
Giovanni
G
Maggiano
Nicola
N
Habib
Aida
A
Ricerca
Bianca M
BM
Barbarotto
Elisa
E
Patrono
Carlo
C
Zauli
Giorgio
G
D000328:Adult; D001842:Bone and Bones / Q000166:cytology; D002478:Cells, Cultured; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D004900:Erythroblasts / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D004920:Erythropoiesis; D005260:Female; D005312:Fetal Blood; D005786:Gene Expression Regulation; D006801:Humans; D007527:Isoenzymes; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D013929:Thromboxane B2 / Q000096:biosynthesis
D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D012333:RNA, Messenger; D013929:Thromboxane B2; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone