Regulation of Human Polymorphonuclear Leukocytes Functions by the Neuropeptide Pituitary Adenylate Cyclase-Activating Polypeptide after Activation of MAPKs Export

@article{citeulike:5734875, abstract = {Anti-inflammatory activities of pituitary adenylate cyclase-activating protein (PACAP) are mediated in part through specific effects on lymphocytes and macrophages. This study shows that in human polymorphonuclear neutrophils (PMNs), PACAP acts as a proinflammatory molecule. In PMNs, vaso-intestinal peptide/PACAP receptor 1 (VPAC-1) was the only receptor found to be expressed by RT-PCR. Using VPAC-1 Ab, we found that VPAC-1 mRNA was translated into proteins. In PMNs, PACAP increases cAMP, inositol triphosphate metabolites, and calcium. It activates two of the three members of the MAPK superfamily, the ERK and the stress-activated MAPK p38. U73122, an inhibitor of phospholipase C (PLC), inhibits PACAP-induced ERK activation, whereas p38 MAPK phosphorylation was unaffected. Using specific pharmalogical inhibitors of ERK (PD098059) and p38 MAPK (SB203580), we found that PACAP-mediated calcium increase was ERK and PLC dependent and p38 independent. PACAP primes fMLP-associated calcium increase; it also primes fMLP activation of the respiratory burst as well as elastase release, these last two processes being ERK and PLC dependent and p38 MAPK independent. PACAP also increases membrane expression of CD11b and release of lactoferrin and metallo proteinase-9 (MMP-9). These effects were PLC dependent (CD 11b, lactoferrin, MMP-9), ERK dependent (CD 11b, lactoferrin, MMP-9), and p38 dependent (CD11b, lactoferrin). We conclude that PACAP is a direct PMN activator as well as an effective PMN priming agent that requires PLC, ERK, and p38 MAPK activities.}, author = {Harfi, Issam and D'Hondt, Stephanie and Corazza, Francis and Sariban, Eric}, citeulike-article-id = {5734875}, citeulike-linkout-0 = {http://www.jimmunol.org/cgi/content/abstract/173/6/4154}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15356166}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15356166}, day = {15}, journal = {J Immunol}, keywords = {inositol, mmp}, month = {September}, number = {6}, pages = {4154--4163}, posted-at = {2009-09-07 14:15:23}, priority = {4}, title = {Regulation of Human Polymorphonuclear Leukocytes Functions by the Neuropeptide Pituitary Adenylate Cyclase-Activating Polypeptide after Activation of MAPKs}, url = {http://www.jimmunol.org/cgi/content/abstract/173/6/4154}, volume = {173}, year = {2004} }

TY - JOUR ID - citeulike:5734875 L3 - citeulike-article-id:5734875 N2 - Anti-inflammatory activities of pituitary adenylate cyclase-activating protein (PACAP) are mediated in part through specific effects on lymphocytes and macrophages. This study shows that in human polymorphonuclear neutrophils (PMNs), PACAP acts as a proinflammatory molecule. In PMNs, vaso-intestinal peptide/PACAP receptor 1 (VPAC-1) was the only receptor found to be expressed by RT-PCR. Using VPAC-1 Ab, we found that VPAC-1 mRNA was translated into proteins. In PMNs, PACAP increases cAMP, inositol triphosphate metabolites, and calcium. It activates two of the three members of the MAPK superfamily, the ERK and the stress-activated MAPK p38. U73122, an inhibitor of phospholipase C (PLC), inhibits PACAP-induced ERK activation, whereas p38 MAPK phosphorylation was unaffected. Using specific pharmalogical inhibitors of ERK (PD098059) and p38 MAPK (SB203580), we found that PACAP-mediated calcium increase was ERK and PLC dependent and p38 independent. PACAP primes fMLP-associated calcium increase; it also primes fMLP activation of the respiratory burst as well as elastase release, these last two processes being ERK and PLC dependent and p38 MAPK independent. PACAP also increases membrane expression of CD11b and release of lactoferrin and metallo proteinase-9 (MMP-9). These effects were PLC dependent (CD 11b, lactoferrin, MMP-9), ERK dependent (CD 11b, lactoferrin, MMP-9), and p38 dependent (CD11b, lactoferrin). We conclude that PACAP is a direct PMN activator as well as an effective PMN priming agent that requires PLC, ERK, and p38 MAPK activities. IS - 6 JF - J Immunol EP - 4163 TI - Regulation of Human Polymorphonuclear Leukocytes Functions by the Neuropeptide Pituitary Adenylate Cyclase-Activating Polypeptide after Activation of MAPKs VL - 173 SP - 4154 KW - inositol KW - mmp AU - Harfi, Issam AU - D'Hondt, Stephanie AU - Corazza, Francis AU - Sariban, Eric PY - 2004/09/15/ UR - http://www.jimmunol.org/cgi/content/abstract/173/6/4154 ER -