Arachidonic Acid Oxygenation Products Research Articles

Arachidonic acid metabolites mediate early burn edema.

Standard burns were sequentially produced on the backs of Sprague-Dawley rats at 0, 1, 2, and 2 1/2 hr, followed by the IV injection of Evans blue dye. All animals were killed at 3 hr, and burns evaluated by wet/dry weight ratios, and Evans blue extravasation scored 1-4 by two observers. Five groups of rats were compared to controls. Rats made neutropenic by exposure to 137cesium showed no significant difference in wet/dry weight ratio or Evans blue extravasation compared to controls. At 1 1/2 hr four other groups were treated with various inhibitors of arachidonic acid metabolism including ibuprofen, a cyclo-oxygenase inhibitor; FPL 55712, a leukotriene (LT) receptor antagonist; ketoconazole, an inhibitor of thromboxane (Tx) synthetase; and lodoxamide, a calcium channel inhibitor. All treated groups showed significant reduction of Evans blue dye extravasation. Wet/dry weight ratios were significantly reduced in rats treated with FPL 55712 and ketoconazole before or after burning. These data support the postulate that oxygenation products of arachidonic acid, particularly Tx and LT, are important mediators in early burn edema.

Serologic and immunochromatographic detection of oxygenated polyenoic acids in [formula omitted][formula omitted][formula omitted][formula omitted

Acetone extracts of Euglena gracilis Klebs var. bacillaris Cori contain several lipoxygenase and cyclooxygenase products as measured by radioimmunoassay. Three times more of the serologically active products are found in cells grown in the dark than in cells grown in the light. Lack of coincidence of their retention times on high performance liquid chromatography with authentic oxygenation products of arachidonic acid suggest that most of the serologically active compounds are derivitives of polyenoic fatty acids other than arachidonic acid. Several fractions react with anti-12-hydroxyarachidonic acid (an antiserum that recognizes mono- and di-hydroxyarachidonic acids). Three of these fractions have UV absorption spectra characteristic of conjugated trienes.

The role of arachidonic acid oxygenation products in pain and inflammation.

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More

The Role of Arachidonic Acid Oxygenation Products in Pain and Inflammation

The Role of Arachidonic Acid Oxygenation Products in Pain and Inflammation

Detection of compounds immunologically related to arachidonic acid transformation products in extracts of invertebrates

Organic extracts of Terpios zeteki , a sponge from the phylum Porifera, Aplysia californica and Helix aspersa , two species from the phylum Molluscs, and Arbacia , the sea urchin, from the phylum Echino-dermata, contained compounds that appeared by radioimmunoassays to be HETE, PGE 2, PGF 2α, and 6-keto-PGF 1α, the non-enzymatic hydrolytic product of PGI 2. However, lack of coincidence of their retention times on HPLC with authentic oxygenation products of arachidonic acid suggested that most of the immunologically active compounds were derivatives of arachidonic acid metabolites or products derived from polyunsaturated fatty acids other than arachidonic acid.

A functional deficiency of C1q in 3 family members

S 1313 A FUNCTIONAL DEFICIENCY OF Clq IN 3 FAMILY MEMBERS. A.J. Hannema, H.C. K/h-Nelemans, C.E. Hack’, C. Mallbe, H.P.T. van He/den, A.J.M. Eerenberg-Belmer; Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam and St. Antonius Hospital, Utrecht, The Netherlands. Two sisters and a brother from one family are described with a funtionally deficient Clq. All 3 had suffered from glomerulonephritis during childhood. The 2 sisters had recently a SLE-like disease (butterfly erythema, oral ulceration, arthralgia, alopecia, grand mal seizure in one, and leukopenia in the other.) The brother is apparently healthy although a microscopic hematuria is present. By radial immunodiffusion (RID) with anti-Clq a faint but measurable precipitation ring was found only after staining the plate. By double immunodiffusion a partial identity of this Clq with normal Clq was found. The abnormal Clq gave a line of complete identity with reduced and alkylated Clq. This abnormal Clq was found in all 3 patients. The sera from the sisters had no hemolytic activity, however the brother had a CH50 titer of 24% of normal serum. The hemolytic defect was restored by the addition of purified Clq to the serum. Less than O.l%, of Clq was present-in the sera from the sisters, the brother had O.l%, as measured by hemolytic assay. Clr, Cls and Cl-inhibitor were normal or increased as measured by RID. Aggregated IgG (AHG) did not activate Cl in any of the sera, as was demonstrated by the Cl-inhibitor complex assay. Also, no C4 or C3 were fixed to AHG, though the abnormal Clq showed some affinity for AHG. Both defects were restored by the addition of Clq to the sera. The abnormal Clq sedimented in the 4.6 S position. This pattern was not changed in the presence of Ca-ions. The abnormal Clq probably represents the 3 chains A, B and C of Clq. A CT-INHIBITOR-COMPLEX ASSAY (INCA): A METHOD TO DETECT Cl ACTIVATION IN VITRO AND IN VIVO C.E. Hack*, A.J. Hannema, A.J.M. Eerenberg-Belmer, TA. Out and R.C. Aalberse. Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, The Netherlands. We developed a radioimmunoassay (the i 6 hrs: 10.76; 12 hrs: 17.97; 18 hrs: 19.81 nglml). Release of PgE and TxB2 was almost abolished if the C3b preparation was passed over an anti-C3 immunosorbent column or if 0.5 fig/ml indomethacin was added to cultures simultaneously with C3b. Addition of the Fab fragment of anti-C3 IgG did not diminish the stimulatroy action of C3b nor did Fab of unrelated IgG. In conclusion, C3b is a stimulator of the snythesis and release of arachidonic acid oxygenation products in peritoneal macrophages. Our findings lend further support to the view that C3b is a factor capable of modulating macrophage functions and thereby affecting activities of cooperating and bystander cells.

Phagocytosis-Stimulated Macrophages. Production of Prostaglandins and SRS-A, and Prostaglandin Effects on Macrophage Activation

Quiescent mouse peritoneal macrophages which phagocytose, and which respond to phagocytosis with a sudden elevation in hexose monophosphate shunt activity, immediately release into the medium oxygen metabolites, arachidonic acid oxygenation products, and lysosomal hydrolases. Such cells subsequently differentiate and acquire the properties of inflammatory macrophages. The latter process appears to be under the control of prostaglandin E 2and possibly other cyclooxygenase products which are formed as a consequence of phagocytosis and seem to act as feed-back inhibitors.

Biochemical correlates of macrophage activation

ABSTRACT Biological activities induced in macrophages by stimulation are usually paralleled by changes in biochemical parameters, i.e. the production of oxygen metabolites by the respiratory burst, the release of arachidonic acid oxygenation products, the secretion of lytic enzymes, and changes in cell-associated enzyme activities. In this paper we analyze the possibilities to monitor macrophage activation on the basis of these biochemical parameters.

Oxygenation Products of Arachidonic Acid as Mediators of Hypersensitivity and Inflammation

Oxygenation Products of Arachidonic Acid as Mediators of Hypersensitivity and Inflammation

Prostaglandins, arachidonic acid, and inflammation.

The enzymatic oxidation of arachidonic acid has been shown to yield potent pathological agents by two major pathways. Those of the prostaglandin (PG) pathway, particularly PGE2, have been implicated as inflammatory mediators for many years. The discovery and biological activities of thromboxane A2 and prostacyclin as well as a destructive oxygen-centered radical as additional products of this biosynthetic pathway now require these to be considered as potential inflammatory mediators. Like PGE2, their biosynthesis is prevented by nonsteroidal anti-inflammatory agents. More recently, the alternative metabolic route, the lipoxygenase pathway, has been shown to yield a new class of arachidonic acid oxygenation products, called the leukotrienes, which also appear to be important inflammatory mediators. Unlike the prostaglandins, some of which play important roles as biological regulators, the actions of the lipoxygenase products appear to be exclusively of a pathological nature.

The diminished production of arachidonic acid oxygenation products by elicited mouse peritoneal macrophages: possible mechanisms.

The diminished production of arachidonic acid oxygenation products by elicited mouse peritoneal macrophages: possible mechanisms.

Release of mediators from free bronchoalveolar cells: effect of ionophore A23187 and antigen challenge.

The ionophore A23187 stimulated the release of prostaglandins and SRS-A (now identified as leukotriene D4) from guinea-pig bronchoalveolar macrophages. Upon specific antigen challenge of the cells obtained from ovalbumin-sensitized animals or of normal cells preincubated with the serum of sensitized animals, prostaglandins, SRS-A or histamine were undetectable. Furthermore, treatment of "sensitized" cells with the ionophore resulted in a reduced liberation of prostaglandins in comparison to control cells. It is suggested that sensitization produce in bronchoalveolar macrophages some functional alterations of arachidonic acid oxygenation products.

Metabolism of arachidonic acid by platelets: utilization of arachidonic acid by human platelets in presence of linoleic and dihomo-gamma-linolenic acids.

In vitro human platelet prostaglandin synthesis has been studied from added radioactive arachidonic acid (i) as function of substrate concentration, (ii) as function of platelet concentration and (iii) as function of pH. Platelets, as in platelet rich plasma when labelled with arachidonic acid, washed and treated with thrombin, released radioactivity mainly from phosphatidylcholine and phosphatidylinositol. The released radioactivity was mostly accounted for by the formation of the previously identified oxygenation products of arachidonic acid. Platelet utilization or arachidonic acid was also studied in presence of linoleic and dihomo-gamma-linolenic acids, the two essential fatty acids known for antithrombotic effect. At its high concentrations linoleic acid decreased platelet cyclo-oxygenase activity as seen by a decreased formation of endoperoxides from arachidonic acid. Dihomo-gamma-linolenic acid was found to be a mutually competitive substrate with arachidonic acid for the platelet prostaglandin synthetase thus causing reduced utilization of arachidonic acid as shown by measuring the various oxygenation products of arachidonic acid. These two acids were utilized differently by platelet prostaglandin synthetase.

Synthesis and release of oxygenation products of arachidonic acid by mononuclear phagocytes in response to inflammatory stimuli.

Evidence that macrophages secrete products that contribute to the central role played by these cells in chronic inflammation continues to accumulate. These products include hydrolytic enzymes active at either acid or neutral pH, prostaglandins, several components of the complement system, factors affecting the responses of T and B lymphocytes to mitogens, factor(s) causing increased proliferation and collagen synthesis by fibroblasts, pyrogen, and interferon. There is little information available concerning the effect of inflammatory stimuli on the secretion of these products. In the case of two types of macrophage secretory products, namely lysosomal acid hydrolases and prostaglandins, there is a marked dependence of their release on the nature of the stimuli presented to the cells. Zymosan or antigen-antibody complexes, which show potent inflammatory activity, cause the selective release of acid hydrolases from macrophages in a dose- and time-dependent fashion. These stimuli also cause the release of [3H]arachidonic acid from phospholipids, with resultant synthesis and secretion of prostaglandins. On the other hand, latex particles, which have minimal inflammatory activity in vivo, fail to cause selective release of lysosomal enzymes from macrophages and do not cause prostaglandin biosynthesis and secretion. The major products of arachidonic acid oxygenation produced by macrophages appear to be PGE2 and 6-keto PGF1α, the stable metabolite of PGI2.

Role of prostaglandin endoperoxide PGG2 in inflammatory processes.

SINCE the discovery that non-steroidal anti-inflammatory agents (NSAI) are potent inhibitors of prostaglandin synthetase1–3, there has been controversy about the role of primary prostaglandins (PGEs+PGFs=PGs) in inflammatory diseases. A parallel has been demonstrated between the ability of drugs such as indomethacin and aspirin to inhibit cyclo-oxygenase, the initial step leading to the formation of PGs, and anti-inflammatory activity4–6. The failure of administered PGs to fully mimic inflammation processes, however, is not consistent with this concept7,8, and further studies have shown that other products derived from the reaction of cyclo-oxygenase with arachidonic acid (PGG2, PGH2 and thromboxane A2) although quite labile, have biological activities exceeding the potency of the PGs themselves9,10. Since these ephemeral mediators are also subject to regulation by NSAI they too must be considered as potential causal agents of inflammation. We have investigated this possibility by examining the action of several NSAI on the total pattern of arachidonic acid oxygenation products. The results indicate that the endoperoxide PGG2 has a pivotal role in acute inflammation.