Metabolic Patterns in Three Types of Phagocytizing Cells

Oren, Rachel; Farnham, Ann E.; Saito, Kazuhisa; Milofsky, Eva S.; Karnovsky, Manfred L.

doi:10.1083/jcb.17.3.487

Cited by 455 publications

(198 citation statements)

References 15 publications

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“…Alternative activation of macrophages causes the up-regulation of innate immune receptors such as the MR and type I scavenger receptors, and consequently enhances the cell capacity for phagocytosis (6). Even with this increase in phagocytosis, AM have been shown to have a decreased respiratory burst in response to stimuli, compared with blood monocytes (7). This evidence suggests that components within the alveolar space may limit inflammation in the lung by modulating AM production of ROI in response to stimuli.…”

Section: T He Alveolar Macrophage (Am)mentioning

confidence: 88%

Pulmonary Surfactant Protein A Inhibits Macrophage Reactive Oxygen Intermediate Production in Response to Stimuli by Reducing NADPH Oxidase Activity

Crowther

Kutala²,

Kuppusamy³

et al. 2004

The Journal of Immunology

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Alveolar macrophages are important host defense cells in the human lung that continuously phagocytose environmental and infectious particles that invade the alveolar space. Alveolar macrophages are prototypical alternatively activated macrophages, with up-regulated innate immune receptor expression, down-regulated costimulatory molecule expression, and limited production of reactive oxygen intermediates (ROI) in response to stimuli. Surfactant protein A (SP-A) is an abundant protein in pulmonary surfactant that has been shown to alter several macrophage (Mφ) immune functions. Data regarding SP-A effects on ROI production are contradictory, and lacking with regard to human Mφ. In this study, we examined the effects of SP-A on the oxidative response of human Mφ to particulate and soluble stimuli using fluorescent and biochemical assays, as well as electron paramagnetic resonance spectroscopy. SP-A significantly reduced Mφ superoxide production in response to the phorbol ester PMA and to serum-opsonized zymosan (OpZy), independent of any effect by SP-A on zymosan phagocytosis. SP-A was not found to scavenge superoxide. We measured Mφ oxygen consumption in response to stimuli using a new oxygen-sensitive electron paramagnetic resonance probe to determine the effects of SP-A on NADPH oxidase activity. SP-A significantly decreased Mφ oxygen consumption in response to PMA and OpZy. Additionally, SP-A reduced the association of NADPH oxidase component p47phox with OpZy phagosomes as determined by confocal microscopy, suggesting that SP-A inhibits NADPH oxidase activity by altering oxidase assembly on phagosomal membranes. These data support an anti-inflammatory role for SP-A in pulmonary homeostasis by inhibiting Mφ production of ROI through a reduction in NADPH oxidase activity.

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Section: T He Alveolar Macrophage (Am)mentioning

confidence: 88%

Pulmonary Surfactant Protein A Inhibits Macrophage Reactive Oxygen Intermediate Production in Response to Stimuli by Reducing NADPH Oxidase Activity

Crowther

Kutala²,

Kuppusamy³

et al. 2004

The Journal of Immunology

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“…3 The data reported here should be regarded as lower limits for rates of H202 production. The assay measured only H202 that was released from cells and that was not expended in the oxidation of reactants other than scopoletin, including the cells or materials associated with them.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen peroxide release from mouse peritoneal macrophages: dependence on sequential activation and triggering.

Nathan¹,

Root²

1977

The Journal of Experimental Medicine

447

174

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Using a specific and sensitive fluorometric assay, the H2O2 release from as few as 2 X 10(5) mouse peritoneal macrophages could be detected continuously and quantitated. It is emphasized that the assay measured H2O2 release, not production. Induction of H2O2 release required sequential application of two stimuli: the administration of an activating agent to the mice from 4 days to 10 wk before all harvest, and the exposure of the cells in vitro to a triggering agent. BCG was most effective as an activating agent, resulting in peritoneal macrophages which could be triggered to release H2O2 almost as copiously (8 nmol/10(6) macrophages per 5 min) as mouse peritoneal PMN (9 NMOL/10(6) PMN per 5 min). Casein and C. parvum could also serve as activators, but thioglycollate and FCS were ineffective after single injections. PMA was a potent triggering agent, resulting in a maximal rate of H2O2 release after a latency of about 40 s for cells in suspension. Other triggering agents included the ionophore A23187, concanavalin A in the presence of cytochalasin B, and phagocytosis. H2O2 release could be attributed to macrophages and PMN in peritoneal cell suspensions or in preparations of adherent peritoneal cells, but not to lymphocytes. Indirect evidence suggested that the H2O2 detected was formed from superoxide anion. These observations appear to justify renewed interest in the idea that H2O2 may be important in macrohpage antimicrobial and antitumor mechanisms.

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“…Our observations of a similar relationship between serum concentration and activities of pyruvate kinase and cytochrome oxidase suggest the possibility that demand for glycolytic activity and oxygen consumption required for increased endocytic activity could provide a stimulus for changes in pyruvate kinase and cytochrome oxidase activities. In this regard it should be noted that endocytosis is an energy-requiring process involving both glycolysis and oxidative metabolism (3,16).…”

Section: Discussionmentioning

confidence: 99%

Adaptations of Energy Metabolism in the Cultivated Macrophage

Simon

Axline

Horn

et al. 1973

The Journal of Experimental Medicine

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The in vitro differentiation of the monocyte into the larger, structurally more complex, functionally more active macrophage is accompanied by an increase in glycolytic activity as well as an increased dependence on aerobic metabolism (1-3). There is little information regarding the factors that regulate these changing patterns of energy metabolism during differentiation. In view of previous observations that environmental constituents have a profound effect on endocytosis (4, 5), one of the principal functional activities of the macrophage, it was of interest to determine if such factors exert a similar influence on the sources of energy provision. Pyruvate kinase activity provides an accurate index to glycolytic capacity (6-8) and cytochrome oxidase an index to mitochondrial oxygen utilization (9, 10). The effects of serum and hypoxia on pyruvate kinase and cytochrome oxidase activities of the cultivated macrophage are examined in the present report. Materials and MethodsAnimals.--Male mice (25-30 g) of the NCS/PA strain were used in all experiments. The newly designated strain was derived from the NCS (pathogen-free) mice of The Rockefeller University and has been maintained since 1970 as an outbred colony at the Veterans Administration Hospital, Palo Alto, Calif.In Vitro Cultivation of Mononuclear Phagocytes.--Cells were harvested from the peritoneal cavity of unstimulated mice in heparinized, phosphate-buffered saline pH 7.4 by techniques described previously (1, 5). A 10 ml sample of cells (3.0 X 106/ml) in Medium 199 (Schwarz/ Mann, Division of Becton, Dickinson and Co., Orangeburg, N.Y.) containing 20% newborn calf serum (N-BCS) 1 (Grand Island Biological Co., Berkeley, Calif.) was dispensed to each 30 cm 2 T flask, incubated for 60 rain at 37°C, and washed twice in Medium 199 as previously described (5). Cells were reincubated in fresh Medium 199 containing either 2 or 30% NBCS.At the time of harvest, tissue culture media was removed and monolayers were rinsed three

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Metabolic Patterns in Three Types of Phagocytizing Cells

Cited by 455 publications

References 15 publications

Pulmonary Surfactant Protein A Inhibits Macrophage Reactive Oxygen Intermediate Production in Response to Stimuli by Reducing NADPH Oxidase Activity

Pulmonary Surfactant Protein A Inhibits Macrophage Reactive Oxygen Intermediate Production in Response to Stimuli by Reducing NADPH Oxidase Activity

Hydrogen peroxide release from mouse peritoneal macrophages: dependence on sequential activation and triggering.

Adaptations of Energy Metabolism in the Cultivated Macrophage

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