muramidase and 5-hydroxy-6-8-11-14-eicosatetraenoic-acid

Studies were made on the effects of stilbene derivatives isolated from medicinal plants on arachidonate metabolism and degranulation in human polymorphonuclear leukocytes (PMN-L). Resveratrol (3,4',5-trihydroxystilbene) isolated from the roots of Reynoutria japonica was found to inhibit the 5-lipoxygenase products 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE), 5,12-dihydroxy-6,8,10,14-eicosatetraenoic acid (5,12-diHETE) and leukotriene C4(LTC4); its concentrations for 50% inhibition (IC50) were 8.90 x 10(-6) M, 6.70 x 10(-6) M and 1.37 x 10(-6) M, respectively. The IC50 of 5-HETE, 5,12-diHETE and LTC4 formations of synthetic 3,3',4-trihydroxystilbene were 5.90 x 10(-6) M, 6.30 x 10(-7) M and 8.80 x 10(-7) M, respectively. Moreover, they inhibited the release of lysosomal enzyme such as lysozyme and beta-glucuronidase induced by calcium ionophore A 23187 from human PMN-L at 10(-3)-10(-4) M.

Topics: Arachidonic Acid; Autoradiography; Calcimycin; Cell Degranulation; Cyclic AMP; Fatty Acids, Unsaturated; Glucuronidase; Humans; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Leukotriene C4; Lysosomes; Muramidase; Neutrophils; Plant Roots; Plants, Medicinal; Resveratrol; Stilbenes; Structure-Activity Relationship

5(S)-Hydroxyicosatetraenoate stimulates human polymorphonuclear neutrophils (PMNs) to raise their cytosolic calcium. It also potentiates the cells' degranulation responses to platelet-activating factor and diacylglycerols. We synthesized 5(R)-hydroxyicosatetraenoate and found it to be 20-100-fold weaker than the natural isomer in these assays. Thus, the arachidonic acid metabolite activates PMNs by a stereospecific possibly receptor-mediated mechanism.

Topics: Calcium; Diglycerides; Exocytosis; Glucuronidase; Humans; Hydroxyeicosatetraenoic Acids; Muramidase; Neutrophils; Platelet Activating Factor; Stereoisomerism; Tetradecanoylphorbol Acetate

Human neutrophils incorporated 5-hydroxy-E,Z,Z,Z-6,8,11,14-eicosatetraenoic acid (5-HETE) into cellular triglyceride and phospholipid. They also metabolized 5-HETE into a novel, extracellularly released derivative, 5,20-dihydroxy-E,Z,Z,Z-6,8,11,14-eicosatetraenoic acid (5,20-diHETE). 5,20-diHETE formation predominated at higher substrate concentrations and longer incubation intervals. In the absence of added 5-HETE, 1 X 10(8) neutrophils stimulated with 20 microM ionophore A23187 produced up to 243 ng of 5,20-diHETE, indicating that both endogenously formed and exogenously added substrate could be oxidized at carbon 20. 5,20-diHETE was about 10- to 100-fold weaker than 5-HETE in enhancing human neutrophil degranulation responses to platelet-activating factor. omega-Oxidation appears to be a general enzymatic mechanism for inactivation of arachidonic acid metabolites.

Topics: Calcimycin; Glucuronidase; Humans; Hydroxyeicosatetraenoic Acids; Muramidase; Neutrophils; Oxidation-Reduction; Phospholipids; Platelet Activating Factor; Spectrum Analysis; Triglycerides

Thrombin, a highly specific coagulation factor, can rapidly trigger lysozyme release from human neutrophils without concomitant activation of the 5-lipoxygenase pathway. This activation was not dependent on the presence of extracellular calcium. Since thrombin also induces the release of hemostatic and inflammatory metabolites from platelets and mast cells, it is proposed that it plays a significant role in amplification of the inflammatory response.

Topics: Arachidonic Acid; Arachidonic Acids; Calcium; Humans; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Kinetics; Muramidase; Neutrophils; Thrombin

Diglyceride activators of protein kinase C (i.e., 1-0-myristoyl-, 1-0-palmitoyl-, and 1-0-oleoyl-2-acetylglycerol) interacted synergistically with an arachidonate metabolite, 5-hydroxyicosatetraenoate, to stimulate neutrophil degranulation and superoxide anion generation. Contrastingly, combinations of 15-hydroxyicosatetraenoate with the glycerides or 5-hydroxyicosatetraenoate with a dialkylglyceride (1-0-hexadecyl-2-ethylglycerol) produced no such synergy. The data support a view of stimulus-response coupling wherein protein kinase C is activated in parallel with the mobilization of arachidonate. Respective products of these events, e.g., phosphorylated proteins and hydroxyicosatetraenates, then interact to mediate function.

Topics: Arachidonic Acid; Arachidonic Acids; Cytoplasmic Granules; Diglycerides; Drug Synergism; Enzyme Activation; Glucuronidase; Humans; Hydroxyeicosatetraenoic Acids; Muramidase; Neutrophils; Protein Kinase C; Protein Kinases; Superoxides

Platelet-activating factor (AAGPC) and two of its structural analogues degranulated human neutrophils with respective potencies that were increased up to 100 to 1000-fold by 16 nM to 5 microM of 5-L-hydroxyeicosatetraenoate (5-L-HETE). 5-rac-HETE had similar actions but 8-rac-HETE was without effect. Furthermore, 5-L-HETE did not influence the degranulating actions of C5a, A23187 or a formalated oligopeptide chemotactic factor and none of the HETEs, by themselves, caused degranulation. Thus, 5-L-HETE and AAGPC selectively interact to induce degranulation. Since these products rapidly form in stimulated PMNs, they may serve as potentiator and agonist, respectively, to transduce biological signals into cell function.

Topics: Arachidonic Acids; Calcimycin; Complement C5; Complement C5a; Drug Synergism; Glucuronidase; Humans; Hydroxyeicosatetraenoic Acids; Muramidase; N-Formylmethionine; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Oligopeptides; Platelet Activating Factor; Time Factors

Topics: Arachidonic Acids; Cell Adhesion; Cell Movement; Chemotaxis; Cytochalasin B; Glucuronidase; Humans; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Muramidase; Neutrophils; SRS-A; Structure-Activity Relationship