Two new formylated peptides able to activate chemotaxis and respiratory burst selectively as tools for studying human neutrophil responses.
Two new For-Met-Leu-Phe-OH (FMLP) methyl ester analogues, For-Thp-Leu-Ain-OMe [Thp1, Ain3] and For-Met-delta zLeu-Phe-OMe [delta zLeu2], able to activate selectively chemotaxis and superoxide anion (O2-) release, respectively modulate intracellular cyclic AMP (cAMP) levels in different ways. FMLP and [delta zLeu2] enhance human neutrophil cAMP levels per se, and this effect is potentiated by Ro 201724, a non-xanthinic phosphodiesterase (PDE) inhibitor, whereas it is counteracted by 3-isobutyl-1-methyl-xanthine (IBMX), a blocker of both phosphodiesterase and adenosine receptors. In contrast, [Thp1, Ain3] is ineffective. However, no formylated peptides influence cAMP phosphodiesterase activity. Neutrophil preincubation with Ro 201724 or IBMX drastically reduces chemotaxis and superoxide anion (O2-) production triggered by peptides. Our results suggest that: (1) peptide-induced cAMP increase is probably indirect, and due mainly to the action on adenosine-sensitive adenylate cyclase; (2) formylated peptide, endowed solely with chemotactic activity is unable to increase neutrophil cAMP concentration; (3) cAMP elevation may represent a feed-back mechanism to inhibit the physiological responses induced by formylated peptides.
Ferretti
M E
ME
Istituto di Fisiologia Generale, Università degli Studi di Ferrara, Italy.
Spisani
S
S
Pareschi
M C
MC
Buzzi
M
M
Cavallaro
R
R
Traniello
S
S
Reali
E
E
Torrini
I
I
Paradisi
M P
MP
Zecchini
G P
GP
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D002465:Cell Movement; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D004952:Esters; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D016897:Respiratory Burst / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism
D004952:Esters; D013481:Superoxides; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015056:1-Methyl-3-isobutylxanthine