Hyporesponsiveness of murine myeloid progenitor cells to glucan following its repeated administration.
A moderate marrow granulocytic hyperplasia developed after 4 injections of glucan (soluble derivative carboxymethylglucan) administered to mice at 3-4-day intervals. However, when evaluating the response of the marrow granulocyte-macrophage colony-forming cells (GM-CFC) to the fifth glucan injection given in the repetitive treatment schedule, the development of hyporesponsiveness of these cells was found, contrary to the stimulatory action of a single glucan injection. In addition, the prompt increase in serum granulocyte-macrophage colony-stimulating activity occurring after a single glucan injection, and proposed to upregulate myelopoiesis, was absent in mice treated with glucan repeatedly. A joint administration of glucan with diclofenac, an inhibitor of prostaglandin synthesis, was able to enhance the GM-CFC response to a single glucan injection, probably due to the removal of the downregulation action of prostaglandins on these progenitor cells. However, a repeated administration of diclofenac with glucan did not reduce substantially the development of GM-CFC hyporesponsiveness. Thus, the results suggest that the GM-CFC hyporesponsiveness or tolerance to repeated glucan injections was induced by weakening the mechanisms of positive control mediated by the serum colony-stimulating activity.
Pospísil
M
M
Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno.
Vacek
A
A
Hofer
M
M
Viklická
S
S
Pipalová
I
I
Sandula
J
J
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000096:biosynthesis; D004008:Diclofenac / Q000494:pharmacology; D005936:Glucans / Q000494:pharmacology*; D006098:Granulocytes / Q000187:drug effects / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology*; D006965:Hyperplasia; D008262:Macrophage Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D047071:beta-Glucans
D000276:Adjuvants, Immunologic; D003115:Colony-Stimulating Factors; D005936:Glucans; D047071:beta-Glucans; D004008:Diclofenac; C033363:beta-1,3-glucan