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Diazepam‐binding inhibitor‐derived peptides induce intracellular calcium changes and modulate human neutrophil function
Author(s) -
Cosentino Marco,
Marino Franca,
Cattaneo Simona,
Di Grazia Laura,
Francioli Cristina,
Fietta Anna Maria,
Lecchini Sergio,
Frigo Gianmario
Publication year - 2000
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.67.5.637
Subject(s) - chemotaxis , phagocytosis , extracellular , biology , intracellular , microbiology and biotechnology , receptor , respiratory burst , superoxide , calcium in biology , calcium , n formylmethionine leucyl phenylalanine , biochemistry , medicine , enzyme
We studied the effects of two diazepambinding inhibitor (DBI)‐derived peptides, triakonta‐tetraneuropeptide (DBI 17–50, TTN) and eiksoneuropeptide (DBI 51–70, ENP), on cytosolic free Ca 2+ concentrations ([Ca 2+ ] i ), chemotaxis, superoxide anion (O) generation, and phagocytosis in human neutrophils. Both TTN and ENP induced a rapid and transient rise of [Ca 2+ ] i . The effect of TTN depended on the presence of extracellular Ca 2+ , whereas the effect of ENP also persisted after extracellular Ca 2+ chelation. TTN induced neutrophil chemotaxis, stimulated O generation, and enhanced phagocytosis. ENP did not affect cell migration and oxidative metabolism but enhanced phagocytosis. Both peptides modulated N ‐formylmethionyl‐leucyl‐phenylalanine‐ and phorbol myristate acetate‐induced O generation. Because neutrophils express benzodiazepine receptors of the peripheral type (pBRs) and DBI‐derived peptides may interact with such receptors, we investigated the possible role of pBRs in TTN‐ or ENP‐induced effects. The synthetic pBR ligand RO 5‐4864 increased [Ca 2+ ] i through extracellular Ca 2+ influx and this effect was prevented by the pBR antagonist PK‐11195. RO 5‐4864, however, was ineffective on neutrophil migration and O generation and only slightly affected phagocytosis. Moreover, PK‐11195 delayed the [Ca 2+ ] i rise induced by TTN but did not significantly affect its extent, and had no effect on the [Ca 2+ ] i rise induced by ENP. We conclude that DBI‐derived peptides induce [Ca 2+ ] i changes and modulate neutrophil function mainly through pBR‐independent pathways. In view of the wide cell and tissue distribution of DBI in the brain and in peripheral organs, modulation of neutrophil function by DBI‐derived peptides may be relevant for both the neuroimmune network and the development and regulation of the inflammatory processes. J. Leukoc. Biol. 67:637–643; 2000.