Stimulus-specific production of cyclooxygenase and lipoxygenase metabolites of arachidonic acid by bovine alveolar macrophages (original) (raw)
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Arachidonic acid metabolism in bovine alveolar macrophages
Inflammation, 1986
The production of lipoxygenase metabolites of arachidonic acid was studied in bovine alveolar macrophages (BAM). Unstimulated macrophages produced sinai1 amounts of LTB4 (0.2 + 0.2 ng/106 BAM) but monohydroxyeicosatetraenoic acids (5-, 12-, and 15-HETE) usually were not detectable. Both exogenous arachidonic acid and the calcium ionophore A23187 induced production of LTB 4, 5~, 12-, and 15-HETE, of which 60-80% was 5-HETE. Combined challenge of BAM with both exogenous al~chidonic acid and A23187 was more effective in the production of these metabolites than with either stimulus alone. The generation of the peptidoleukotfienes LTC4, LTD4, and LTE4 by BAM could not be detected under these in vitro conditions. Our results demonstrate that bovine alveolar macrophages produce similar lipoxygenase metabolites of arachidonic acid in response to A23187, as do human alveolar macrophages stimulated with the same agonist.
Comparison of arachidonate metabolism by alveolar macrophages from bighorn and domestic sheep
Inflammation, 1991
We have defined the metabolites of arachidonic acid (AA) secreted by alveolar macrophages (AMs) of bighorn sheep and domestic sheep in response to three agents: calcium ionophore A23187, phorbol myristate acetate (PMA), and opsonized zymosan. Cells were labeled with [3H]AA prior to stimulation and 11 tritiated metabolites, including prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs), and hydroxyeicosatetraenoic acids (HETEs), were detected and quantitated by high-performance liquid chromotography and radiometry. Zymosan stimulation resulted in the release of significantly elevated quantities (P < 0.05), of LTB4, [5(S), 12(R)-dihydroxy-6,14-cis-8, lO-trans-eicosatetraenoic acid], 5-HETE, [5(S)-hydroxyeicosatetraenoic acid], and the nonenzymatic isomers of LTB4, [LTB I, 5(S), 12(R)-6-trans-LTB4] and LTB II, [5(S), 12(S)-6-trans-LTB4], from domestic sheep AM when compared to bighorn sheep AM. Phorbol myristate acetate (PMA) stimulation released significantly elevated quantities (P < 0.04), of TXB2, (thromboxane B2), HHT, [12(S)-12-hydroxy-5,8,10 heptadecaenoic acid], LTB I, LTB II, and 15-HETE, [15(S)-hydroxyeicosatetraenoic acid] from domestic sheep AMs when compared to bighorn sheep AMs. However, after A23187 challenge, only 15-HETE was significantly elevated (P < 0.04) in domestic sheep AMs when compared to bighorn sheep AMs. These clear differences in AA metabolism of AMs obtained from bighorn and domestic sheep in response to three different agonists suggest not only different control mechanisms for lung metabolism of AA in the two species, 43
Arachidonic acid metabolism is altered in sarcoid alveolar macrophages
Clinical immunology and …, 1987
rages produce various arachidonic acid (AA) metabolites which may either enhance or suppress inflammatory processes. We investigated AA metabolite production by alveolar macrophages (AMs) from 11 patients with pulmonary sarcoidosis and 9 normal volunteers. We assessed the production of both cyclooxygenase products (prostaglandin (PC) E,, thromboxane B, (TXB,), PGF,,, and 6-keto-PGF,,) and lipoxygenase products (leukotrienes (LT) and hydroxyeicosatetraenoic acids (HETEs)) in AM cultures. We found that sarcoid AMs produced less PGE,, TXB,, 6-keto-PGF,,, and HETEs in both the unstimulated and the calcium ionophore-stimulated states compared with normal AMs. Sarcoid AMs also produced less PGF,, and LTs in the unstimulated state after 1 hr of incubation, but following calcium ionophore stimulation, these differences did not achieve statistical significance. We conclude that sarcoid AMs have a reduced capacity to produce AA metabolites compared with that of normal AMs. 8~
Age-dependent change in arachidonic acid metabolic capacity in rat alveolar macrophages
IUBMB Life, 1999
Arachidonic acid (AA) metabolism was assessed in cultured alveolar macrophages (AM) obtained from newborn (10 days old) and adult (2 months and 4 months old) rats. The AMs were stimulated with the calcium ionophore, A23187 (10~tM). The released radiolabelled AA metabolites were measured by thin layer chromatography. The results showed that among different aged rats, the synthesis of 5-1ipoxygenase (5-LO) metabolites, LTB4, LTC4, LTD4 and 5-HETE were increased with age inspite of similar levels of [14C]AA release. In response to A23187, 5-LO metabolic capacity of 2 and 4 months old adult rat A_Ms were increased 21fold and 34-fold, respectively, compared with 10 days old rat AMs. As the metabolic capacity increased, the release of prostaglandins and thromboxane B2 tended to decrease markedly. Newborn rats (10 days old) AM, at the initial developmental stage, did not produce a noticeable amount of 5-LO metabolites which, conceivably, contribute to high susceptibility of neonatal lung to infection.
Virus-Induced Enhancement of Arachidonate Metabolism by Bovine Alveolar Macrophages In Vitro
Journal of Leukocyte Biology, 1989
Virus infection of alveolar macrophages both in vivo and in vitro has been associated with a variety of changes in cellular function. Some of these changes are identical to the effects that arachidonate-derived mediators, prostaglandins, leukotrienes, and hydroxyeicosatetraenoic acids, have on macrophage function. Virus infection of macrophages has been previously shown to increase the output of some arachidonate metabolites, most notably PGE2. However, the effect of virus infection on arachidonate metabolism in general has not been well described. In our experiments, primary cultures of alveolar macrophages obtained from normal cattle by bronchoalveolar lavage, were infected in vitro with parainfluenza type 3 virus. At days 0 to 4 post-infection (p.i.) these cells were labelled with 3H-arachidonic acid and stimulated with either serum-coated zymosan, the calcium ionophore A23187, or phorbol myristate acetate. The complete spectrum of arachidonate-derived metabolites was determined ...
Mechanisms of Ageing and Development, 2001
The incidence of infectious respiratory diseases increases with aging. Resident alveolar macrophages (AMs) and recruited leukocytes (PMNL) mediate cellular defense against bacterial infections in the lung, and phagocytosis and lipid mediator synthesis are important components of their antimicrobial capacity. The objective of this study was to determine if either phagocytic capacity or lipid mediator generation declines with normal aging, in either AMs or PMNL recruited to a site of inflammation. The F344xBN rat hybrid has a lower incidence of pathologies associated with aging, particularly up to 20 months; animals aged 6, 12 and 18 months were chosen to evaluate changes associated with normal aging. As previously reported for peripheral blood leukocytes, phagocytosis by recruited PMNL declined with aging: recruited PMNL from 18 months rats showed a significantly decreased capacity to phagocytose live Klebsiella pneumoniae bacteria, compared to PMNL from 6 months rats. Surprisingly, however, the phagocytic capacity of AMs increased with aging: the phagocytic index of AMs from 18 months rats was more than three times that of AMs from 6 months rats. The capacity of AMs and recruited PMNL to release arachidonic acid www.elsevier.com/locate/mechagedev Abbre6iations: 5-HETE, 5-hydroxyeicosatetraenoic acid; AM, alveolar macrophage; LT, leukotriene; PG, prostaglandin; PMNL, polymorphonuclear leukocyte.
Cellular Immunology, 1980
This study examines the contribution of the lipoxygenase products of arachidonic acid, termed hydroxy-eicosatetraenoic acids or HETEs, to the neutrophil chemotactic activity elaborated by rabbit alveolar macrophages. The predominant neutrophil chemotactic activity released by phagocytosing alveolar macrophages exhibits a molecular weight of 300-800, as assessed by Sephadex G2.5 filtration, and cochromatographs with defined HETE standards on silica gel H thin-layer plates. The chemotactic factors generated by the alveolar macrophages were identified by gas chromatography and mass spectroscopy as SHETE and I I-HETE. The quantities of 5-HETE and I I-HETE released from alveolar macrophages at I and 4 hr were increased up to five-fold by phagocytosis. Incubation of the alveolar macrophages with the lipoxygenase inhibitor 5,8,l l,14-eicosatetraynoic acid prior to phagocytosis eliminated completely the stimulation of the generation of both the HETEs and the neutrophil chemotactic activity. The neutrophil chemotactic activity produced by phagocytosing alveolar macrophages thus is attributable largely to SHETE and I I-HETE.