Mannuronan enhances survival of lethally irradiated mice and stimulates murine haematopoiesis in vitro.
Mannuronan (poly-beta-(1-->4)-D-mannuronate or poly-M), produced by Pseudomonas aeruginosa as a mucoid exopolysaccharide, has previously been shown to exhibit immunostimulating activity. The authors investigated the in vivo and in vitro effects of mannuronan on murine haematopoiesis. 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 stimulated with mannuronan produced high levels of interleukin(IL)-1, IL-6 and colony stimulating activity. Mannuronan alone did not have any colony stimulating activity on GM-CFC, BFU-E, Mix-CFC or HPP-CFC progenitors in clonogenic assays, but acted synergistically with suboptimal amounts of growth factors on GM-CFC, Mix-CFC and HPP-CFC colony formation. Limiting dilution analysis showed that 1 of 423 bone marrow cells formed colonies in response to suboptimal GM-CSF plus mannuronan compared to 1 of 592 for suboptimal GM-CSF alone. The primitive Lin-Sca-1+ haematopoietic progenitors showed increased day 10 colony size in the presence of mannuronan in single cells assays. These stimulating effects of mannuronan on haematopoiesis may prove to have clinical importance.
Halaas
O
O
Institute of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, Trondheim.
Olsen
W M
WM
Veiby
O P
OP
Løvhaug
D
D
Skjåk-Braek
G
G
Vik
R
R
Espevik
T
T
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000464:Alginates / Q000494:pharmacology*; D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D003114:Colony-Forming Units Assay; D005260:Female; D005354:Fibrosarcoma; D020723:Glucuronic Acid; D006410:Hematopoiesis / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects; D016298:Hematopoietic Cell Growth Factors / Q000096:biosynthesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006603:Hexuronic Acids; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D011828:Radiation Chimera / Q000276:immunology; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000464:Alginates; D016298:Hematopoietic Cell Growth Factors; D006603:Hexuronic Acids; D007375:Interleukin-1; D015850:Interleukin-6; D020723:Glucuronic Acid