Hematopoietic augmentation by a beta-(1,4)-linked mannan.
CARN 750 (injectable acemannan) is a polydispersed beta-(1,4)-linked acetylated mannan isolated from the Aloe barbadensis plant. It has multiple therapeutic properties including activity in wound repair and as a biological agent for the treatment of neoplasia in animals as well as the ability to activate macrophages. We report herein that CARN 750 directly or indirectly has significant hematoaugmenting properties. We observed that the subcutaneous administration of CARN 750 significantly increases splenic and peripheral blood cellularity, as well as hematopoietic progenitors in the spleen and bone marrow as determined by the interleukin-3-responsive colony-forming unit culture assay and the high-proliferative-potential colony-forming-cell (HPP-CFC) assay (a measure of primitive hematopoietic precursors) in myelosuppressed (7 Gy) C57BL/6 mice. The greatest hematopoietic effect was observed following sublethal irradiation in mice receiving 1 mg CARN 750/ animal, with less activity observed at higher or lower doses. Further, CARN 750, following daily injection, has activity equal to or greater than the injection of an optimal dose of granulocyte-colony-stimulating factor (G-CSF) in myelosuppressed mice. In this comparison, significantly greater activity was observed in the splenic and peripheral blood cellularity, and in the frequency and absolute number of splenic HPP-CFC as compared to the mice receiving G-CSF at 3 micrograms/animal. CARN 750, when administered to myelosuppressed animals, decreased the frequency of lymphocytes with a concomitant significant increase in the frequency of polymorphonuclear leukocytes (PMN). However, owing to the increased cellularity, a significant increase in the absolute number of PMN, lymphocytes, monocytes and platelets was observed, suggesting activity on multiple cell lineages. The latter is the primary difference in activity as compared to G-CSF which has activity predominantly on PMN.
Egger
S F
SF
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-5660, USA.
Brown
G S
GS
Kelsey
L S
LS
Yates
K M
KM
Rosenberg
L J
LJ
Talmadge
J E
JE
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001773:Blood Cells / Q000166:cytology / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002236:Carbohydrate Conformation; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects; D006413:Hematopoietic System / Q000166:cytology / Q000187:drug effects*; D008351:Mannans / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D014916:Whole-Body Irradiation
D000276:Adjuvants, Immunologic; D008351:Mannans; C058414:acemannan