A 'pure' chemoattractant formylpeptide analogue triggers a specific signalling pathway in human neutrophil chemotaxis.
As it has not yet been established whether the second messengers involved in the neutrophil response have identical or specific signalling requirements for each physiological function, protein kinase C (PKC) isoforms and mitogen activated protein kinases (MAPKs) were studied in human chemotaxis triggered by the full agonist for-Met-Leu-Phe-OMe (fMLP-OMe) and the 'pure' chemoattractant for-Thp-Leu-Ain-OMe [Thp1,Ain3] analogue. Experiments were performed in the presence or absence of extracellular Ca2+, known to be an important modulator of second messengers. Our data demonstrate that specific PKC beta1 translocation and p38 MAPK phosphorylation are strongly associated with the chemotactic response of the neutrophils triggered by both peptides, while Ca2+ is not necessary for chemotaxis to occur. PKC and MAPK inhibitors were used in Western blotting assays and in cell locomotion experiments to investigate if the MAPK signalling pathway was controlled by PKC activation. The most important finding emerging from this study is that PKC and MAPK activate the chemotactic function of human neutrophils by two independent pathways.
Spisani
Susanna
S
Dipartimento di Biochimica e Biologia Molecolare, Università degli Studi di Ferrara, Italy.
Falzarano
Sofia
S
Traniello
Serena
S
Nalli
Marianna
M
Selvatici
Rita
R
D015153:Blotting, Western; D002630:Chemotactic Factors / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009504:Neutrophils / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000502:physiology*
D002630:Chemotactic Factors; D010455:Peptides; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases