Stimulation of the oxidative metabolism of polymorphonuclear leucocytes by the calcium ionophore A23187

Schell-Frederick, E.

doi:10.1016/0014-5793(74)81056-2

Cited by 65 publications

(18 citation statements)

References 15 publications

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“…These include oxidative metabolism (Schell-Frederick, 1974;Romeo, Zabucchi, Miani & Rossi, 1975), lysosomal enzyme release (Zabucchi, Soranzo, Rossi & Romeo, 1975; Smith & Ignarro, 1975) and chemiluminescence (Weidemann,Peskar,Wrogemann, Rietschel,Staudinger & Fischer, 1978). The ionophore also induces the release of chemotactic factors (Czarnetzki, K6nig & Lichtenstein, 1975), causes PMN aggregation (O'Flaherty, Kreutzer, Showell, Becker & Ward, 1978) and stimulates the release from PMNs of prostaglandins and thromboxane B2 (Knapp, Oelz, Roberts, Sweetman, Oates & Reed, 1977;Weidemann et al, 1978;Wentzell & Epand, 1978).…”

Section: Introductionmentioning

confidence: 99%

Calcium Ionophore A23187 Induces Release of Chemokinetic and Aggregating Factors From Polymorpho‐nuclear Leucocytes

Bray

Ford‐Hutchinson

Shipley

et al. 1980

British J Pharmacology

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Rat and human polymorphonuclear leucocytes (PMNs) when exposed to calcium ionophore A23187 10 μm release products which cause aggregation of rat PMNs and chemokinesis of human PMNs. Aggregating and chemokinetic activities are rapidly generated; maximal release occurs after 4 min, and can be detected in dilutions of the supernatant of up to 1:1000. Generation of aggregating and chemokinetic activities is inhibited by nordihydroguaiaretic acid 10−4 to 10−7 m, 5,8,11,14‐eicosatetraynoic acid 10−4 and 10−5 m, BW 755C 10−4 m and benoxaprofen 10−4 m, all compounds known to inhibit lipoxygenase pathways of arachidonic acid (AA) metabolism. Conventional non‐steroidal anti‐inflammatory agents, such as aspirin and indomethacin, inhibited little or not at all the generation of these activities. We conclude that the aggregating and chemokinetic activities induced by A23187 represent generation of biologically active products of lipoxygenase pathways of AA metabolism.

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Section: Introductionmentioning

confidence: 99%

Calcium Ionophore A23187 Induces Release of Chemokinetic and Aggregating Factors From Polymorpho‐nuclear Leucocytes

Bray

Ford‐Hutchinson

Shipley

et al. 1980

British J Pharmacology

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“…Several studies have also demonstrated a stimulatory effect of ionophore A23187 on the formation of thromboxane B2 (13,14) and prostaglandins (13)(14)(15) in leukocytes. It is of interest in this context that ionophore A23187 has also been found to stimulate some phagocytosis-associated responses of leukocytes-i.e., oxidative metabolism (16,17), chemiluminescence (14), and secretion of lysosomal enzymes (18,19).…”

mentioning

confidence: 99%

Arachidonic acid metabolism in polymorphonuclear leukocytes

Borgeat

Samuelsson

1979

Proc. Natl. Acad. Sci. U.S.A.

698

235

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Addition of arachidonic acid and the divalent cation ionophore A23187 to a suspension of human peripheral blood polymorphonuclear leukocytes led to the formation of 8,11,8,11, and (5S,8,10, A method based on high-pressure liquid chromatography has been developed for assay of these metabolites. The addition of arachidonic acid to human polyinorphonuclear leukocytes always resulted in formation of the isomeric monohydroxy acids. However, cells prepared from blood of different subjects were found to vary with respect to formation of the 5,12-dihydroxy acid. Addition of the ionophore alone strongly stimulated the formation of the 5-monohydroxy acid and more specifically the 5,12-dihydroxy acid from endogenous arachidonic acid. In all experiments performed the formation of the 5-hydroxy acid and the 5,12-dihydroxy acid was maximally stimulated when both arachidonic acid and the ionophore were added to the incubation mixture. Under these conditions, stimulation of 40-fold or more of the formation of both compounds was observed. The data demonstrate that, in addition to causing release of endogenous substrate, the ionophore also activated the enzymatic system involved in the further transformations of arachidonic acid. This finding raises the possibility that this pathway of arachidonic acid metabolism is involved in the biological response (e.g., release of lysosomal enzymes, the slow reacting substance of anaphylaxis, and chemotactic factors) of leukocytes to A23187 and other stimuli.Recent studies have indicated that polyunsaturated fatty acids and their metabolites are involved in the functions of leukocytes (1, 2). It was thus reported that two hydroxy acids formed from arachidonic acid-namely, 12-hydroxy-5,8,10,14-icosatetraenoic acid and 12-hydroxy-5,8,10-heptadecatrienoic acid-induced chemotaxis by polymorphonuclear leukocytes (PMNL) (3-5). It was also recently shown that unsaturated fatty acid peroxides, such as arachidonic acid peroxides, stimulate platelet guanyl cyclase activity (6, 7). This last finding might be particularly significant in view of the effects of 3',5'-guanosine monophosphate on lysosomal enzyme release (8, 9) and leukocyte locomotion (10-12). Several studies have also demonstrated a stimulatory effect of ionophore A23187 on the formation of thromboxane B2 (13, 14) and prostaglandins (13)(14)(15) in leukocytes. It is of interest in this context that ionophore A23187 has also been found to stimulate some phagocytosis-associated responses of leukocytes-i.e., oxidative metabolism (16, 17), chemiluminescence (14), and secretion of lysosomal enzymes (18, 19).We have recently demonstrated the formation of two metabolites of arachidonic acid in rabbit peritoneal PMNLnamely, (SS)-hydroxy-6,8,11,14-icosatetraenoic acid (20) and (5S. 12R)-dihydroxy-6,8,10,14-icosatetraenoic acid (21). It was therefore of interest to extend our studies to the metabolism of arachidonic acid in human PMNL. In addition, the effect of ionophore A23187 on the formation of the metabolites has been studied. Our find...

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“…In addition to inducing a CL in resting PMNL, the ionophore was also observed to augment phagocytosis-associated CL evoked by opsonized zymosan. Earlier studies have demonstrated the ability of this agent to stimulate oxidative metabolism in PMNL independently of phagocytosis in a calcium-dependent manner [5,6,9]. Another soluble agent, phorbol myristate acetate (PMA), was reported to stimulate oxidative metabolism and CL in resting PMNL [lo].…”

Section: Discussionmentioning

confidence: 99%

“…One such agent is the divalent cation ionophore A23 187, which has been reported to stimulate oxidative metabolism in resting neutrophils in a calcium-dependent manner [5,6]. This communication describes the calcium-dependent induction of CLin resting human PMNL by ionophore A23 187 and the ability of this agent to modify phagocytosis-associated CL induced by opsonized zymosan.…”

Section: Introductionmentioning

confidence: 99%

Induction of chemiluminescence in human polymorphonuclear leukocytes by the calcium ionophore A23187

et al. 1978

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Stimulation of the oxidative metabolism of polymorphonuclear leucocytes by the calcium ionophore A23187

Cited by 65 publications

References 15 publications

Calcium Ionophore A23187 Induces Release of Chemokinetic and Aggregating Factors From Polymorpho‐nuclear Leucocytes

Calcium Ionophore A23187 Induces Release of Chemokinetic and Aggregating Factors From Polymorpho‐nuclear Leucocytes

Arachidonic acid metabolism in polymorphonuclear leukocytes

Induction of chemiluminescence in human polymorphonuclear leukocytes by the calcium ionophore A23187

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