Hemoregulatory peptide (HP5b) dimer effects on normal and malignant cells in culture

Abstract

The dimer of the hemoregulatory peptide HP5b has been investigated for biological effects on various cell types in culture including mouse granulocyte-macrophage colony forming units (CFU-GM) from agar and murine long-term bone marrow culture (LTBMC). While CFU-GM were significantly stimulated in both systems, mitogen activation of mouse T, B and natural killer (NK) cells was not affected. Peptide treated mouse 3T3 fibroblasts reached a higher saturation density than controls; otherwise no effect was seen. A series of malignant cell lines was also tested. On a human glioblastoma cell line (GaMg) and rat glioma cell line (BT5C) a slight but significant stimulatory effect was found, while human mammary carcinoma cells (MCF7) were not affected. On SC1 mouse lymphoma cells a slight stimulation of cell growth was seen during the first part of exponential growth. Since HP5b acts as a stimulator for stromal cell secretion of other growth factors, supernatants from a human bone marrow stromal cell line stimulated with HP5b were tested on various cell lines. The effects of the supernatants on cell growth of the tested cell lines were not affected by HP5b treatment. Taken together with available in vivo data, the results indicate that the hemoregulatory peptide is a selective stimulator of myelopoiesis.

Haemopoietic stem cells: their heterogeneity and regulation

“…This is likely to be due in large part to the ability of the pentapeptide to form a dimeric variant through generation of disulphide bonds involving the cysteine residues on two apposing monomers. Interestingly this dimer is inactive as an inhibitor but is active as a stimulator of murine and human GM-CFC proliferation and the response to this stimulatory variant is also biphasic with maximal activity being seen at 10-9 M (Frostad et al 1993). This tendency to dimerise has hampered preclinical studies with the pentapeptide, however, recently stable monomeric and dimeric variants of this molecule have been generated.…”