In vivo modulation of hematopoiesis by a novel hematoregulatory peptide

Louis Pelus, A. G. King, Hal Broxmeyer, P. L. DeMarsh, S. R. Peteway, P. K. Bhatnagar

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The hematoregulatory peptide dimer, HP5B, enhances myelopoiesis by stimulating stromal cell cytokine production. However, the disulfide bridge of this peptide is susceptible to reduction, leading to the formation of monomeric pentapeptide, HP5, a direct-acting inhibitor of myelopoiesis. We have replaced the disulfide (S-S)d bond of HP5B dimer with an isosteric ethylene (CH2-CH2) group, creating a new, nonreducible, metabolically more stable peptide (SK and F 107647). This novel peptide was tested in vitro and in vivo for hematopoietic effects. In vitro, SK and F 107647 has no direct colony-stimulating activity (CSA). Stimulation of murine stromal cells with SK and F 107647 results in production and release of CSA at concentrations as low as 0.01 ng/mL, at lest 10-fold lower than observed with HP5B dimer. Injection of SK and F 107647 in normal mice results in a two- to six-fold increase in serum CSA, which becomes maximal at 6 hours postinjection. Administration of peptide daily over 4 days (q.d.x4) by both parenteral and oral routes results in significant increases in absolue numbers of granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells, as well as stimulating their cel cycle rates. A doubling in day 8 CFU-S was also observed in SK and F 107647-treated mice. Continuous subcutaneous (s.c.) infusion of SK and F 107647 in femorally cannulated rats demonstrated modest but significant elevation of peripheral blood neutrophil and monocyte counts within 7 days. SK and F 107647 representssd a novel synthetic hematoregulatory peptide that shares biological and/or modulation activities with natural hematopoietic cytokines.

Original languageEnglish (US)
Pages (from-to)239-247
Number of pages9
JournalExperimental Hematology
Volume22
Issue number3
StatePublished - 1994
Externally publishedYes

Fingerprint

Hematopoiesis
Peptides
Myelopoiesis
Stromal Cells
Disulfides
Cytokines
Myeloid Progenitor Cells
Subcutaneous Infusions
Granulocyte-Macrophage Progenitor Cells
Erythroid Precursor Cells
SK&F 107647
Granulocytes
Monocytes
Neutrophils
Stem Cells
Macrophages
Injections
Serum

Keywords

  • Cytokines
  • Hematopoiesis
  • Hematoregulatory peptide
  • SK and F 107647

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Pelus, L., King, A. G., Broxmeyer, H., DeMarsh, P. L., Peteway, S. R., & Bhatnagar, P. K. (1994). In vivo modulation of hematopoiesis by a novel hematoregulatory peptide. Experimental Hematology, 22(3), 239-247.

In vivo modulation of hematopoiesis by a novel hematoregulatory peptide. / Pelus, Louis; King, A. G.; Broxmeyer, Hal; DeMarsh, P. L.; Peteway, S. R.; Bhatnagar, P. K.

In: Experimental Hematology, Vol. 22, No. 3, 1994, p. 239-247.

Research output: Contribution to journalArticle

Pelus, L, King, AG, Broxmeyer, H, DeMarsh, PL, Peteway, SR & Bhatnagar, PK 1994, 'In vivo modulation of hematopoiesis by a novel hematoregulatory peptide', Experimental Hematology, vol. 22, no. 3, pp. 239-247.
Pelus L, King AG, Broxmeyer H, DeMarsh PL, Peteway SR, Bhatnagar PK. In vivo modulation of hematopoiesis by a novel hematoregulatory peptide. Experimental Hematology. 1994;22(3):239-247.
Pelus, Louis ; King, A. G. ; Broxmeyer, Hal ; DeMarsh, P. L. ; Peteway, S. R. ; Bhatnagar, P. K. / In vivo modulation of hematopoiesis by a novel hematoregulatory peptide. In: Experimental Hematology. 1994 ; Vol. 22, No. 3. pp. 239-247.
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AB - The hematoregulatory peptide dimer, HP5B, enhances myelopoiesis by stimulating stromal cell cytokine production. However, the disulfide bridge of this peptide is susceptible to reduction, leading to the formation of monomeric pentapeptide, HP5, a direct-acting inhibitor of myelopoiesis. We have replaced the disulfide (S-S)d bond of HP5B dimer with an isosteric ethylene (CH2-CH2) group, creating a new, nonreducible, metabolically more stable peptide (SK and F 107647). This novel peptide was tested in vitro and in vivo for hematopoietic effects. In vitro, SK and F 107647 has no direct colony-stimulating activity (CSA). Stimulation of murine stromal cells with SK and F 107647 results in production and release of CSA at concentrations as low as 0.01 ng/mL, at lest 10-fold lower than observed with HP5B dimer. Injection of SK and F 107647 in normal mice results in a two- to six-fold increase in serum CSA, which becomes maximal at 6 hours postinjection. Administration of peptide daily over 4 days (q.d.x4) by both parenteral and oral routes results in significant increases in absolue numbers of granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells, as well as stimulating their cel cycle rates. A doubling in day 8 CFU-S was also observed in SK and F 107647-treated mice. Continuous subcutaneous (s.c.) infusion of SK and F 107647 in femorally cannulated rats demonstrated modest but significant elevation of peripheral blood neutrophil and monocyte counts within 7 days. SK and F 107647 representssd a novel synthetic hematoregulatory peptide that shares biological and/or modulation activities with natural hematopoietic cytokines.

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