In vivo modulation of hematopoiesis by a novel hematoregulatory peptide

L. M. Pelus, A. G. King, H. E. Broxmeyer, P. L. DeMarsh, S. R. Peteway, P. K. Bhatnagar

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 - Mar 18 1994

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

Fingerprint Dive into the research topics of 'In vivo modulation of hematopoiesis by a novel hematoregulatory peptide'. Together they form a unique fingerprint.

Cite this