thromboxane-b2 and Leukemia--Lymphoid

We have isolated and characterized a novel human and rat organic anion transporter subtype, OATP-D. The isolated cDNA from human brain encodes a polypeptide of 710 amino acids (Mr 76,534) with 12 predicted transmembrane domains. The rat clone encodes 710 amino acids (Mr 76,821) with 97.6% amino acid sequence homology with human OATP-D. Human and rat OATP-D have moderate amino acid sequence homology with LST-l/rlst-1, the rat oatp family, the prostaglandin transporter, and moatl/MOAT1/KIAA0880/OATP-B. Phylogenetic tree analysis revealed that OATP-D is branched in a different position from all known organic anion transporters. OATP-D transports prostaglandin E1 (Km 48.5 nM), prostaglandin E2 (Km 55.5 nM), and prostaglandin F2,, suggesting that, functionally, OATP-D encodes a protein that has similar characteristics to those of the prostaglandin transporter. Rat OATP-D also transports prostaglandins. The expression pattern of OATP-D mRNA was abundant mainly in the heart, testis, brain, and some cancer cells. Immunohistochemical analysis further revealed that rat OATP-D is widely expressed in the vascular, renal, and reproductive system at the protein level. These results suggest that OATP-D plays an important role in translocating prostaglandins in specialized tissues and cells.

Topics: Alprostadil; Amino Acid Sequence; Animals; Anions; Blotting, Northern; Brain Chemistry; Burkitt Lymphoma; Dinoprostone; DNA, Complementary; HeLa Cells; HL-60 Cells; Humans; K562 Cells; Leukemia, Lymphoid; Lung Neoplasms; Melanoma; Molecular Sequence Data; Oocytes; Organic Anion Transporters; Rats; RNA, Messenger; Xenopus laevis

Prostaglandins have been implicated as possible modulators of the proliferation and differentiation of neoplastic cells. The aim of this work was to determine 6-keto-PGF1 alpha and TXB2 concentrations in the blood plasma and in the supernatant of 96 hour PHA stimulated and unstimulated leukaemic cell cultures of chronic lymphocytic leukaemia patients. 62 patients with CLL classified to the 1st or 4th stage according to RAI, and 23 healthy individuals were investigated. The blastogenic transformation was measured by the standard tritiated thymidine method. The quantity of 6-keto-PGF1 alpha and TXB2 was estimated by the isotopic method using a RIA-kit. In the 4th stage of CLL a low value of blastogenic transformation was observed, whereas in the 1st stage, the values were similar to those of the control group. It was shown that in the 4th stage of the disease an increase in the 6-keto-PGF1 alpha concentrations occurs in the blood plasma and the culture supernatant together with a significant decrease in TXB2 in the culture supernatant, whereas in the 1st stage a significant decrease in the 6-keto-PGF1 alpha as compared with those of the control group is noted. These results may indicate on antagonistic action of PGI2 and TXB2 in leukaemia cell proliferation.

Topics: 6-Ketoprostaglandin F1 alpha; Cells, Cultured; Culture Media; Humans; Leukemia, Lymphoid; Lymphocyte Activation; Lymphocytes; Phytohemagglutinins; Thromboxane B2

This study was undertaken to test the effects of certain arachidonate derivatives, PGF2 alpha, PGI2 and TxB2 on in vitro bone marrow granulocyte colony growth (CFU-C) in leukemia patients receiving maintenance chemotherapy and in normal controls. The addition of PGF2 alpha did not result in increased numbers of colonies, but it did cause a shift in the size of the colonies so that there was a significant increase in larger colonies (P less than 0.001) and significantly fewer small colonies (P less than 0.05) as compared to untreated samples. Of the prostenoids tested in a Tris-buffered system, PGI2 affected the greatest increase in CFU-C (P less than 0.01) followed by PGF2 alpha (P less than 0.05) whereas 6-keto-PGF1 alpha (the stable hydrate of PGI2) did not affect colony growth. Time-response curves revealed a linear growth pattern for PGF2 alpha with a peak at 10 days, whereas there was a 6-day growth lag with PGI2 followed by linear growth with a peak at 13 days. TxB2 added to cultures significantly reduced the number of bone marrow CFU-C at all doses tested. The prostanoid effects on CFU-C derived from leukemic patients on maintenance chemotherapy and from normal individuals were identical in every respect.

Topics: Adolescent; Adult; Child; Child, Preschool; Colony-Forming Units Assay; Dinoprost; Epoprostenol; Female; Humans; Infant; Leukemia, Lymphoid; Male; Prostaglandins F; Stem Cells; Thromboxane B2; Thromboxanes