Formylpeptides trigger selective molecular pathways that are required in the physiological functions of human neutrophils.
For-Met-Delta(z)Leu-Phe-OMe ([Delta(z)Leu(2)]) is a conformationally restricted for-Met-Leu-Phe-OMe (fMLP-OMe) analogue able to discriminate between different responses of human neutrophils. In contrast, [Delta(z)Leu(2)] significantly activates the transduction pathways-involving Ca(2+), inositol phosphate, and cyclic AMP (cAMP) enhancement, as is the case with the full agonist fMLP-OMe. Here, we have studied the specific involvement of protein kinase C (PKC) isoforms and mitogen activated protein kinases (MAPKs) in the presence or absence of extracellular Ca(2+), being the cation clearly involved in the activation of neutrophils by fMLP. A strong correlation has been found between PKC isoforms, MAPKs and the selective physiological functions by [Delta(z)Leu(2)]-activated neutrophils. In a calcium-free condition, our data suggest that the failure of PKC beta1 translocation and of p38 MAPK phosphorylation by the analogue refers to its inability to induce chemotaxis, and that the failure by both fMLP-OMe and [Delta(z)Leu(2)] to evoke extracellular response kinase 1 and 2 (ERK1/2) phosphorylation would suggest a reduction in superoxide anion production.
Selvatici
Rita
R
Dipartimento di Medicina Sperimentale e Diagnostica, Sezione Genetica Medica, Via L Borsari 46, Università degli Studi di Ferrara, 44100 Ferrara, Italy.
Falzarano
Sofia
S
Traniello
Serena
S
Pagani Zecchini
Giampiero
G
Spisani
Susanna
S
D002118:Calcium / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004789:Enzyme Activation; D006801:Humans; D066298:In Vitro Techniques; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D013481:Superoxides
D013481:Superoxides; C080504:formyl-methionyl-delta(Z)-dehydroleucyl-phenylalanine methyl ester; D009240:N-Formylmethionine Leucyl-Phenylalanine; C042932:formylmethionyl-leucyl-phenylalanine methyl ester; D011493:Protein Kinase C; D020929:Mitogen-Activated Protein Kinase Kinases; D002118:Calcium