Modulation of neutrophil function by the tripeptide feG.
BACKGROUND
Neutrophils are critical in the defense against potentially harmful microorganisms, but their excessive and inappropriate activation can contribute significantly to tissue damage and a worsening pathology. Through the release of endocrine factors submandibular glands contribute to achieving a balance in neutrophil function by modulating the state of activation and migratory potential of circulating neutrophils. A putative hormonal candidate for these effects on neutrophils was identified as a heptapeptide named submandibular gland peptide T (SGP-T; sequence = TDIFEGG). Since the tripeptide FEG, derived from SGP-T, and its D-amino acid analogue feG had similar inhibitory effects on inflammatory reactions, we investigated the effects of feG on human and rat neutrophil function.


RESULTS
With human neutrophils feG had no discernible effect on oxidative burst or phagocytosis, but in picomolar amounts it reduced PAF-induced neutrophil movement and adhesion, and the binding of CD11b by 34% and that of CD16b close to control values. In the rat feG (10-11M) reduced the binding of CD11b and CD16 antibodies to PAF-stimulated circulating neutrophils by 35% and 43%, respectively, and at 100 micrograms/kilograms intraperitoneally feG reduced neutrophil in vivo migration by 40%. With ovalbumin-sensitized rats that were challenged with antigen, feG inhibited binding of antibodies against CD16b but not CD11b, on peritoneal leukocytes.


CONCLUSIONS
The inhibitory effect of feG on neutrophil movement may be mediated by alterations in the co-stimulatory molecules CD11b and CD16.
Mathison
Ronald D
RD
Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, T2N 4N1, Canada. rmathiso@ucalgary.ca
Befus
A Dean
AD
Davison
Joseph S
JS
Woodman
Richard C
RC
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001773:Blood Cells / Q000276:immunology; D039481:CD11b Antigen / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D009842:Oligopeptides / Q000494:pharmacology*; D010537:Peritoneum / Q000166:cytology; D010587:Phagocytosis; D051381:Rats; D017452:Receptors, IgG / Q000276:immunology; D013481:Superoxides / Q000378:metabolism
D000906:Antibodies; D039481:CD11b Antigen; D015815:Cell Adhesion Molecules; D009842:Oligopeptides; D017452:Receptors, IgG; C114891:tripeptide FEG; D013481:Superoxides