Characterization of eosinophil cell activation by peptides. Differential effects of substance P, melittin, and FMET-Leu-Phe.
The ability of three different peptides, substance P (SP), FMLP and melittin, to activate eosinophils purified from the peritoneal cavity of human serum-treated guinea pigs was investigated. Degranulation (eosinophil peroxidase, EPO), oxidative burst (O2-), [Ca2+]i mobilization, and arachidonic acid metabolism (thromboxane B2, TXB2) were used as indices of eosinophil activation. SP (100 nM to 100 microM), FMLP (1 to 100 microM) and melittin (10 nM to 100 microM) induced EPO release but only FMLP (1 to 100 microM) led to an elevation of [Ca2+]i. The melittin- and SP-induced EPO secretion occurred at both cytotoxic and noncytotoxic concentrations as assessed by lactate dehydrogenase release. In addition, the effect of SP was not inhibited by the SP analogue (D-Pro4, D-Trp7,9,10)SP(4-11) and SP failed to promote the generation and subsequent release of TXA2. In contrast, FMLP (10 to 100 microM) stimulated the release of TXB2 from guinea pig eosinophils that was selectively inhibited by pretreatment of the cells with BOC-FMLP. On an equimolar basis (1 microM), melittin was approximately fivefold more active at promoting TXB2 release than FMLP. The results indicate that eosinophils respond to the three peptides, SP, melittin, and FMLP in differential fashion. We conclude that activation of guinea pig eosinophils by FMLP is likely to be receptor-mediated whereas the actions of SP and melittin may act through nonspecific peptide-membrane phospholipid interactions.
Department of Thoracic Medicine, Brompton Hospital, London, U.K.
C
C
Kroegel
M A
MA
Giembycz
P J
PJ
Barnes
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004804:Eosinophils / Q000201:enzymology / Q000502:physiology*; D006168:Guinea Pigs; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008555:Melitten / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D015288:Neurokinin A / Q000494:pharmacology; D010529:Peritoneal Cavity / Q000166:cytology; D010544:Peroxidases / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D013928:Thromboxane A2 / Q000378:metabolism
D013481:Superoxides; D008555:Melitten; D013373:Substance P; D013928:Thromboxane A2; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015288:Neurokinin A; D007770:L-Lactate Dehydrogenase; D010544:Peroxidases; D002118:Calcium