Inhibition of ornithine decarboxylase activity decreases polyamines and suppresses DNA synthesis in human colonic lamina propria lymphocytes.
Ornithine decarboxylase (ODC) and the polyamines are essential for cell proliferation in a variety of cells including lymphocytes. In this study, we investigated the potential role of ODC and polyamines in human colonic lamina propria lymphocytes (LPL) compared to peripheral blood lymphocytes (PBL). Our results show that con A stimulation of LPL and PBL was associated with marked increases in ODC and polyamines. The specific inhibitor of ODC, alpha-difluoromethylornithine (DFMO), resulted in a complete inhibition of ODC activity and depletion of putrescine, spermidine and spermine levels. DFMO also suppressed DNA synthesis of LPL and PBL by up to 48% and 62% respectively. This antiproliferative effect was reversed by adding back the polyamines putrescine (1 mM), spermidine (10 microM) or spermine (10 microM) to the culture medium. We conclude that ODC and the polyamines are important for human LPL proliferation, and hence may play a role in human mucosal immune function.
Elitsur
Y
Y
Department of Pediatrics, Marshall University School of Medicine, Huntington, WV 25701.
Strom
J
J
Luk
G D
GD
D000368:Aged; D015317:Biogenic Polyamines / Q000378:metabolism*; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis; D000518:Eflornithine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology; D008214:Lymphocytes / Q000378:metabolism*; D008875:Middle Aged; D065108:Ornithine Decarboxylase Inhibitors; D011700:Putrescine / Q000378:metabolism; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000378:metabolism
D015317:Biogenic Polyamines; D065108:Ornithine Decarboxylase Inhibitors; D013096:Spermine; D004247:DNA; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine