MANNURONAN ENHANCES SURVIVAL OF LETHALLY IRRADIATED MICE AND STIMULATES MURINE HEMATOPOIESIS IN-VITRO

Mannuronan (poly-beta-(1-->4)-D-mannuronate or poly-M), produced by Ps eudomonas aeruginosa as a mucoid exopolysaccharide, has previously bee n shown to exhibit immunostimulating activity. The authors investigate d the in vivo and in vitro effects of mannuronan on murine haematopoie sis. In vivo, prophylactic (-24 h, intraperitoneal) administration of mannuronan enhanced survival of lethally irradiated mice from zero day 40 survivors (NaCl) to 20, 80 and 70% survival at 0.5, 1 and 2 mg/kg bw mannuronan, respectively. In vitro, primary stromal cultures stimul ated with mannuronan produced high levels of interleukin(IL)-1, IL-6 a nd colony stimulating activity. Mannuronan alone did not have any colo ny stimulating activity on GM-CFC, BFU-E, Mix-CFC or HPP-CFC progenito rs in clonogenic assays, but acted synergistically with suboptimal amo unts of growth factors on GM-CFC, Mix-CFC and HPP-CFC colony formation . Limiting dilution analysis showed that 1 of 423 bone marrow cells fo rmed colonies in response to suboptimal GM-CSF plus mannuronan compare d to 1 of 592 for suboptimal GM-CSF alone. The primitive Lin(-)Sca-(1) + haematopoietic progenitors showed increased day 10 colony size in th e presence of mannuronan in single cell assays. These stimulating effe cts of mannuronan on haematopoiesis may prove to have clinical importa nce.