Chemotactic 5-oxo-icosatetraenoic acids activate a unique pattern of neutrophil responses. Analysis of phospholipid metabolism, intracellular Ca2+ transients, actin reorganization, superoxide-anion production and receptor up-regulation.
Neutrophil cell responses and signal pathways elicited by the chemotactic arachidonic acid metabolites (6E, 8Z, 11Z, 14Z)-5-oxo-icosatetraenoic acid and (6E, 8Z, 11Z, 13E)-5-oxo-15-hydroxy-icosatetraenoic acid were studied and compared with those of other chemotaxins. Polyphosphoinositol lipid analysis revealed activation of phosphatidylinositol-biphosphate 3-kinase by both agonists. Experiments with Fura-2 in the presence of EGTA indicated Ca2+ mobilization from intracellular stores by both 5-oxo-icosanoids. A transient actin response and production of small amounts of superoxide anions upon stimulation with both agents was detected. The changes induced by 5-oxo-icosanoids were more moderate and transient than those obtained by other chemotaxins. Desensitization studies indicated cross-desensitization between both 5-oxo-icosanoids, but no interference with the response of other chemotaxins. All cell responses elicited by 5-oxo-icosanoids at concentrations 500-fold higher than the ED50 of other functions did not induce up-regulation of CD11b and N-formyl-peptide receptors at the cell surface, and failed to potentiate N-formyl-peptide-induced superoxide anion production. These results indicate that 5-oxo-icosanoids trigger a unique pattern of neutrophil responses.
Norgauer
J
J
Department of Dermatology, University of Freiburg, Germany.
Barbisch
M
M
Czech
W
W
Pareigis
J
J
Schwenk
U
U
Schröder
J M
JM
D000199:Actins / Q000097:blood / Q000737:chemistry; D015703:Antigens, CD / Q000097:blood; D001095:Arachidonic Acids / Q000494:pharmacology*; D002118:Calcium / Q000097:blood*; D002630:Chemotactic Factors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology*; D015936:Complement C5a / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D007975:Leukotriene B4 / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000097:blood*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010743:Phospholipids / Q000097:blood*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000097:blood*; D013997:Time Factors; D015854:Up-Regulation; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000199:Actins; D015703:Antigens, CD; D001095:Arachidonic Acids; D002630:Chemotactic Factors; D006893:Hydroxyeicosatetraenoic Acids; D016177:Macrophage-1 Antigen; D010743:Phospholipids; D010566:Virulence Factors, Bordetella; D013481:Superoxides; D007975:Leukotriene B4; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D019204:GTP-Binding Proteins; D002118:Calcium