Structural determinants of the eosinophil: chemotactic activity of the acidic tetrapeptides of eosinophil chemotactic factor of anaphylaxis.
The acidic tetrapeptides of ECF-A, Ala/Val-Gly-Ser-Glu, exhibit peak in vitro chemotactic activity for human eosinophils at concentrations of 3 X 10(-8) M to 10(-6) M, and rapidly deactivate eosinophils to homologous and other stimuli at concentrations as low as 10(-10) M. The analogue Leu-Gly-Ser-Glu reaches peak activity at 10(-8)M-10(-7)M, while Phe-Gly-Ser-Glu requires 10(-4)M to elicit a peak response. Although inversion of the order of glycine and serine does not alter the eosinophil chemotactic activity of the tetrapeptides, deletion of glycine increases by 10-fold the concentration required for peak chemotactic activity, indicating the critical nature of the spacing between NH2- and COOH-terminal residues. The substituent COOH-terminal tripeptide, which is only marginally chemotactic, irreversibly suppresses eosinophil chemotactic responsiveness at a concentration 10,000-fold higher than concentrations necessary for deactivation by the intact tetrapeptide. The high concentration of tripeptide required for this cell directed effect, which is assumed to be analogous to deactivation, is attributed to the absence of the NH2-terminal residue which would facilitate effective interaction with the eosinophil. A substituent NH2-terminal tripeptide and amides of the NH2-terminal amino acids, which are devoid of chemotactic and deactivating activities, reversibly inhibit the tetrapeptide stimulus in a dose-response fashion. The additional finding that the NH2-terminal tripeptide protects the eosinophil from deactivation by the intact tetrapeptide confirms that the competitive interaction is stimulus specific.
D000409:Alanine; D000595:Amino Acid Sequence; D000707:Anaphylaxis / Q000276:immunology; D001665:Binding Sites; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004804:Eosinophils / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D008954:Models, Biological; D009504:Neutrophils / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology*; D012995:Solubility; D013329:Structure-Activity Relationship; D014633:Valine
D009842:Oligopeptides; D014633:Valine; D000409:Alanine