Granulocyte-macrophage colony-stimulating factor plays a role in the functional activity of mast cells.
A peptide homologous to a region of murine granulocyte-macrophage colony-stimulating factor (mGM-CSF), P27-38, which was shown to be a GM-CSF antagonist, inhibited the function of serotonin release from murine mast cells. Peptide P27-38 inhibited immunoglobulin E (IgE)-mediated serotonin release in a dose-dependent manner when induced by either specific antigen or anti-IgE antibody. In contrast, non-receptor-mediated release of serotonin by agents such as compound 48/80 or the calcium ionophore A23187 were not affected by the GM-CSF antagonist. Similar effects were observed with GM-CSF-neutralizing antibodies. The inhibitory effect of P27-38 and the neutralizing antibodies on serotonin release could be reversed by the addition of exogenous GM-CSF to the stimulated mast cells, indicating that the inhibitory activity was probably due to an effect on endogenously produced GM-CSF. These findings suggest that GM-CSF produced by stimulated mast cells is involved in the regulation of their activity in an autocrine manner.
Meade
R
R
Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492-7660.
Neddermann
K M
KM
Greenfield
R S
RS
Braslawsky
G
G
Bursuker
I
I
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism
D000906:Antibodies; D010446:Peptide Fragments; D012701:Serotonin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor