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J A Lindgren

Publications and source records attributed to J A Lindgren.

At least 73 records · Page 4Linked to original sources
PubMed1985

Products of the lipoxygenase pathway in human natural killer cell cytotoxicity.

As earlier data suggested the importance of lipoxygenase activation for expression of human NK cell cytotoxicity, four different lipoxygenase inhibitors were tested for suppression of natural killer (NK) cell lysis. All inhibitors were found active at nontoxic concentrations with 50% inhibition at approximately 15 microM for nordihydroguaiaretic acid (NDGA). NK cell lysis could be reconstituted to NDGA-suppressed cells with leukotriene B4 (LTB4), the all-trans isomers 6-trans-LTB4 and 12-epi-6-trans-LTB4, and 20-COOH-LTB4. LTB4 reconstitution was best in the concentration range 1-100 pM and near control levels at both higher and lower concentrations. Herpesvirus Ateles-transformed killer T cells could also be inhibited by NDGA. These data indicate that lipoxygenase activity is required for human NK cell lysis and that several different LTB4-related products can restore NK activity in inhibited cells; they also suggest that the lipoxygenase pathway is present in the killer cell population.

Arachidonate Lipoxygenases↗
PubMed1985

Leukotriene C4 as a mediator of luteinizing hormone release from rat anterior pituitary cells.

This study demonstrates that leukotriene C4, at concentrations in the picomolar range, released luteinizing hormone (LH) but not growth hormone (GH) from dispersed rat anterior pituitary cells. Leukotriene B4, another lipoxygenase pathway product of arachidonic acid, had no effect on LH or GH release. The stimulatory effect of leukotriene C4 could be seen after 0.5 but not after 3 hr of incubation. This was in contrast to the dose-dependent LH-releasing hormone (LHRH)-induced LH release that was not measurable after 0.5 hr but was fully established after incubation for 3 hr. Furthermore, the LH-releasing ability of leukotriene C4 was blocked in the presence of high doses of LHRH. The immunohistochemical analysis revealed leukotriene C4-immunoreactive fibers at all levels of the median eminence, mainly in the lateral parts. These fibers exhibited a marked overlap distribution with LHRH-immunoreactive fibers and elution-restaining experiments revealed identity of at least a large proportion of the leukotriene C4- and LHRH-immunoreactive fibers. Furthermore, cell bodies in the preoptic area contained both leukotriene C4- and LHRH-like immunoreactivities, suggesting localization of these two compounds in the same neurons.

Animals↗
PubMed1985

Second messenger function of arachidonic acid lipoxygenation products in human natural killer cell lysis?

Human natural killer (NK) cells were tested in the presence of several fatty acid oxygenase inhibitors such as nordihydroguaiaretic acid (NDGA), 5,8,11,14-eicosatetraynoic acid, 3-amino-1-m-(trifluoromethyl)-phenyl-2-pyrazoline (BW 755C), and indomethacin. All drugs inhibited NK lysis at the post-target cell-binding level at concentrations that also suppressed lipoxygenation of arachidonic acid, suggesting that such reactivity may be required for effector cell triggering. NDGA gave a 50% NK cell inhibition in the range of 10-30 microM and also suppressed antibody-dependent and lectin-dependent systems. Further evidence of the involvement of arachidonic acid lipoxygenation was found as NK activity could be reconstituted to NDGA-suppressed effector cells with several metabolites such as LTB4, LTB4 analogues, and hydroxyeicosatetraenoic acids lipoxygenated at C-5, C-12, and C-15. Cyclic nucleotides such as cGMP and cAMP could also reconstitute activity with optimal effects at approximately 10(-8) M. The combined evidence is compatible with a model for triggering lysis in which lipoxygenation products have a second messenger function. Whether arachidonic acid lipoxygenation is necessary for effector cells at all different activation/differentiation stages and whether the lipoxygenation products activate guanylic cyclase, protein kinase C, or some other target molecule remain to be further investigated.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1985

Stimulus-specific neutrophil aggregation: evaluation of possible mechanisms for the stimulus-response apparatus.

We have assessed the effects of formyl peptides, leukotrienes, zymosan-activated serum (ZAS), and calcium ionophore A 23187 on the aggregation response of human neutrophils to characterize the mechanisms involved, particularly the possible contribution of the concomitant burst of oxidative metabolism and degranulation. We found that the tested stimuli induced aggregation waves highly characteristic for each agent. With formyl peptides, such as f-Met-Leu-Phe (fMLP), f-Met-Met-Met-Met (fMMMM), and f-Nle-Leu-Phe-Nle-Tyr-Leu (fNLPNTL), peaks appeared after greater than 60 seconds and were followed by a slow disaggregation. In contrast, leukotriene B4 (LTB4) and its omega-oxidized metabolites, 20-OH-LTB4 and 20-COOH-LTB4, induced rapidly occurring peaks that were maximal after 15 to 30 seconds and that were followed by a rapid and marked disaggregation. ZAS induced peak values after 30 to 90 seconds, and disaggregation kinetics were between fMLP and LTB4. A 23187 in high concentrations (10 to 50 mumol/L) elicited biphasic aggregation waves, whereas lower concentrations induced less pronounced and continuous aggregation responses. Superoxide dismutase, catalase, mannitol, and Tiron did not influence any of the aggregation characteristics. Colchicine and indomethacin did have some effects on peak values but not on the characteristic curve profiles, whereas cytochalasin B had a profound effect on the aggregation response for all tested stimuli. Neutrophils from a patient with chronic granulomatous disease exhibited aggregation responses similar to those of controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcimycin↗
PubMed1984

Formation of leukotriene C4 by human leukocytes exposed to monosodium urate crystals.

Monosodium urate (MSU) crystals stimulate the metabolism of arachidonic acid in mixed populations of human leukocytes. Leukocytes exposed to MSU crystals released leukotriene C4. Leukotriene C4 (LTC4) was characterized and detected by high-performance liquid chromatography (HPLC), UV absorption, bioassay with guinea pig ileum, and radioimmunoassay. Results indicate that MSU crystals stimulate the transformation of arachidonic acid and the formation of leukotriene C4 in human leukocytes; an effect inhibited by colchicine. Moreover, they suggest that LTC4 may serve as a mediator of inflammation in crystal-associated diseases.

Chromatography, High Pressure Liquid↗
PubMed1984

Leukotrienes in the rat central nervous system.

Leukotrienes C4, D4, and E4 were isolated after incubation of rat brain tissue in vitro with the ionophore A23187 and arachidonic acid. Identification of the compounds was carried out using high-performance liquid chromatography, radioimmunoassay, and bioassay. Average production of leukotrienes C4, D4, and E4 during 10 min of incubation was estimated to 25, 8, and 0.7 pmol per g of brain tissue (wet weight), respectively. Radioimmunoassay determinations indicated in vitro biosynthesis of leukotriene C4 in most regions of the brain, with the highest levels obtained in the hypothalamus and the median eminence. In slices from the caudate nucleus, ionophore A23187 caused a dose-dependent stimulation of leukotriene C4 formation with maximal effect at 5 microM. Leukotriene C4 synthesis of rat brain tissue was inhibited by 30 microM nordihydroguaiaretic acid. Finally, using the indirect immunofluorescence technique, nerve endings in the median eminence and cell bodies in the preoptic area reacting with antibodies raised against leukotriene C4 were observed.

Animals↗
PubMed1984

Effects of leukotrienes and f-Met-Leu-Phe on oxidative metabolism of neutrophils and eosinophils.

We assessed the effects of several leukotrienes and of f-Met-Leu-Phe on oxygen consumption in neutrophils and on the initial burst of chemiluminescence (CL) in both neutrophils and eosinophils. It was found that f-Met-Leu-Phe initiated 2.6 times higher oxygen consumption in neutrophils than did leukotriene B4 (LTB4). f-Met-Leu-Phe also stimulated five to 10 times more CL from both types of granulocytes than LTB4, which was at least five times more potent than its omega-hydroxylated metabolite, 20-OH-LTB4, whereas the corresponding 20-COOH derivative was effective only in eosinophils. The double dioxygenation product 5(S), 12(S)- DHETE caused no CL. Neutrophils from patients with chronic granulomatous disease did not respond with CL to any of the agents. The peak of CL occurred 50 to 60 sec after the addition of fMLP, whereas the LTB4-associated peak occurred after 5 to 6 sec and then rapidly subsided. The treatment of cells with sodium azide to inhibit the myeloperoxidase system did not change the kinetics or the rapid decline of the LTB4-induced CL. The CL response to LTB4 could be inhibited to 85% by 0.5 microgram/ml of superoxide dismutase, to 72% by 200 mg/ml of catalase, and to 50% by 80 microM of mannitol. The corresponding figures for f-Met-Leu-Phe-induced CL were 80, 58, and 16%, suggesting that, although a substantial part of the CL appears to be due to superoxide ion production, other oxygen radicals are involved in luminol-enhanced CL production. Thus, in contrast to some previous reports that leukotrienes do not stimulate an oxidative metabolic response in granulocytes despite their potent activity as chemotactic factors, our studies show that leukotrienes are definite inducers of granulocyte oxidative metabolism.

Azides↗
PubMed1983

The stimulation of the initiation of DNA synthesis and cell division in Swiss mouse 3T3 cells by prostaglandin F2 alpha requires specific functional groups in the molecule.

Among a number of prostaglandins, PGF2 alpha had the highest specific activity for stimulating the initiation of DNA synthesis in confluent resting Swiss 3T3 cells. At a saturating concentration of 8.5 X 10(-7) M, PGF2 alpha stimulated 21% of the cells to incorporate [ methyl-3H ]thymidine within 28 h. To elicit similar effects, prostaglandins F1 alpha, E1, E2, and D2 were required in 10-fold higher concentrations. Prostaglandins A1, A2, B1, and prostacyclin had no mitogenic activity. Insulin at 10(-8) M enhanced the stimulatory effect of PGF2 alpha and also of prostaglandins F1 alpha, E1, E2, and D2 by increasing the fraction of labeled nuclei. Methyl derivatives of PGF2 alpha were as effective as PGF2 alpha. Epimerization of the hydroxyl group at C-9 abolished the activity of the molecule. In contrast, upon epimerization at C-11 and C-15, some mitogenic activity was retained. In the presence of insulin, the latter molecules were as active as PGF2 alpha. Oxidation of the hydroxyl group at C-15 to a ketone abolished the mitogenic effect, while methyl ether formation led to only a slight loss of activity. Reduction of the delta 13 double bond also led only to a small reduction of activity. Similar differences in the activity of the various prostaglandins and analogues of PGF2 alpha were observed for 2-deoxyglucose uptake and increases in cell number. The relationships between structure and activity of prostaglandins suggest the existence of some specific receptor for PGF2 alpha to confer mitogenic response.

Animals↗
PubMed1983

A sensitive and specific radioimmunoassay for leukotriene C4.

A sensitive and specific radioimmunoassay suitable for direct measurement of leukotriene C4 was developed. Acetylated leukotriene C4 was coupled to polyamino bovine serum albumin using 1-ethyl-3-(3-dimethylamino-propyl) carbodiimide hydrochloride as coupling agent. The conjugate in complete or incomplete Freund's adjuvant was injected into New Zealand white rabbits. At a final antiplasma dilution of 1 : 1050 the lowest detection limit of leukotriene C4 was 0.046 pmol. The antiplasma cross-reacted less than 1% with leukotrienes D4, E4 and F4, while high relative cross-reaction (86-100%) was obtained with leukotrienes C3, C5 and 11-trans leukotriene C4. In experiments where known amounts of leukotriene C4 were added to leukocyte suspensions, 67-100% of the added amount was recovered by the method. The radioimmunoassay was used to study leukotriene C4 formation after stimulation of leukocyte suspensions with the ionophore A23187.

Antibody Specificity↗
PubMed1983

Mechanisms of leukotriene-induced contractions of guinea pig airways: leukotriene C4 has a potent direct action whereas leukotriene B4 acts indirectly.

The leukotrienes (LT's) are a group of arachidonic acid derivatives implicated as mediators of allergic bronchoconstriction and acute inflammation. Tracheal spirals and strips of lung parenchyma from guinea pigs were used under non-flow conditions to characterize the contractions caused by LTA4, LTB4 and LTC4. Cumulative administrations of leukotrienes desensitized the lung strip, whereas non-cumulative dose-response relationships for the leukotrienes and histamine were reasonably parallel. Half maximal contractions of the lung strips were obtained at a final bath concentration of 1 nM for LTC4 and 300 nM for LTA4 or LTB4, as compared with 6 000 nM for histamine. In the trachea, LTC4 was approximately 100 times more potent than LTA4 and histamine. Leukotrienes B4 and C4, but not acetylcholine or histamine, elicited release of the bronchoconstrictive thromboxane A2 from the lung under non-flow conditions. Indomethacin blocked the contractile response to LTB4, whereas the contractile effect of LTC4 remained unaltered. The beta-adrenoceptor agonist isoproterenol and the LTC4 antagonist FPL 55712 attenuated the contraction, but not the release of thromboxane A2, induced by LTC4. Changing to a perifusion technique rendered the lung strips less sensitive to the direct action of LTC4, and released thromboxane A2 now contributed significantly to the contractile response. In addition, the perifusion experiments indicated that LTB4 released histamine as well. We conclude that the chemoattractant LTB4 is an indirectly acting bronchoconstrictor, whereas the slow reacting substance LTC4 contracts the airway muscle by a predominantly direct mechanism. The exquisite bronchoconstrictive activity of LTC4 may be unrelated to its ability to induce formation of thromboxane A2.

Acetylcholine↗
PubMed1983

Effects of novel lipoxygenase products on migration of eosinophils and neutrophils in vitro.

Since it has been suggested that a lipoxygenase product might be specific chemotactic factor for eosinophils, we assessed the stimulating effects of a variety of lipoxygenase products (LTB4, 20-OH-LTB4, 20-COOH-LTB4 and 5(S)12(S)-DHETE) on both neutrophil and eosinophil migration under agarose. LTB4 was the most potent lipoxygenase cytotaxin for neutrophils as well as eosinophils and its stimulating potential for both cell types was similar. The other leukotrienes stimulated migration of neutrophils less than LTB4, whereas eosinophils did not respond. Thus, the previous suggestion that an eosinophil chemotactic factor could be identical with LTB4 was not verified.

Cell Movement↗
PubMed1982

A novel leukotriene produced by stimulation of leukocytes with formylmethionylleucylphenylalanine.

Stimulation of human polymorphonuclear leukocytes with the chemotactic peptide formylmethionylleucylphenylalanine led to the formation of a novel leukotriene: 5(S),12(R)-dihydroxy-6,8,10,14-eicosatetraen-1,20-dioic acid. This dihydroxydicarboxylic acid is derived from omega-oxidation of 5(S),12(R),dihydroxy-6,8,10,14-eicosatetradienoic acid (leukotriene B4). The intermediate 5(S),12(R),20-trihydroxy-6,8,10,14-eicosatetraenoic acid was also isolated from these incubations. The two metabolites of leukotriene B4 exhibit chemotactic properties for human polymorphonuclear leukocytes but are less active in this respect than the parent compound.

Arachidonic Acids↗