Leukocyte‐deactivating factor from macrophages: Partial purification and biochemical characterization. A novel cytokine

Camarero, V C P C; Colepicolo, Pio; Ribeiro, José M. C.; Karnovsky, Manfred L.

doi:10.1002/jcp.1041570111

“…We have recently confirmed these observations in a foreign body granuloma in mice and demonstrated a close similarity between MRP-14 and macrophage deactivating factor (MDF) [14]. MDF is a factor released by epithelioid cells in vitro with the property of deactivating activated macrophages [15,16]. Yet the complex MRP-8/14 is endowed with microbicidal activity when tested on different microorganisms in vitro [9].…”

Section: Introductionmentioning

confidence: 58%

Antinociceptive effect of the calcium-binding protein MRP-14 and the role played by neutrophils on the control of inflammatory pain

Giorgi

¹

,

Pagano

²

,

Dias

³

et al. 1998

Journal of Leukocyte Biology

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Macrophages secrete a variety of chemical mediators that play a central role in the pathophysiology of inflammatory pain. Therefore, the activation or deactivation of these cells in an inflammatory focus could modulate the intensity of the algogenic response. Based on these premises and on our previous demonstration that the calciumbinding protein MRP-14, highly expressed in neutrophils, deactivates activated macrophages in vitro, we decided to investigate the role of MRP-14 and of neutrophils in the control of inflammatory pain in mice. Our results show that this protein is endowed with antinociceptive activity. When tested in the writhing model it was able to inhibit pain response but did not change the behavior of the animals in the hot plate test. This observation indicates that MRP-14 down-regulates inflammatory but not central pain. Using a model of acute neutrophilic peritonitis induced by glycogen, a close correlation between neutrophil migration and antinociception was detected. Surgical adrenalectomy demonstrated that the antinociceptive response induced by glycogen was not due to endogenous liberation of glucocorticoids. The treatment of animals either with a monoclonal antibody anti-MRP-14 or a monoclonal antibody that depletes the animals of neutrophils reverts the antinociceptive response observed in the glycogen-induced peritonitis. These data define the calcium-binding protein MRP-14 as a novel mediator for the control of inflammatory pain and consequently discloses an anti-inflammatory role for the neutrophil. J. Leukoc. Biol. 64: 214-220; 1998.

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“…Thus, synthetic PQQ, tritiated PQQ and DIMPDA, as well as the sizing columns and HPLC methodology used, are described (10). The cells from which the deactivating factor was obtained, the mode of harvesting, the steps of partial purification by ultrafiltration, gel filtration, and reversed-phase HPLC, etc., are described (8,11 These results seem highly suggestive that PQQ has a role in the respiratory burst of neutrophils, but do not represent proof, as discussed below.…”

Section: Methodsmentioning

confidence: 89%

Aspects of the Release of Superoxide by Leukocytes, and a Means by Which This Is Switched off

Karnovsky¹,

Bishop²,

Camerero³

et al. 1994

Environmental Health Perspectives

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Although great progress has been made in understanding the respiratory burst of leukocytes that produce superoxide (0-), it is possible that a component, or components, might have been overlooked. Furthermore, 0°production and its sequels, though cardinal in bactericidal action, might ultimately be damaging to the host's own cells. It is important, therefore, that a biologic mechanism exist to turn off 0°production by stimulated leukocytes. This article offers evidence that methoxatin (P00), a redox-cycling orthoquinone, might be involved in 0°production by leukocytes. This is based on the fact that inhibitors of 0°production, such as diphenylene iodonium (DPI) and 4,5-dimethylphenylene diamine (DIMPDA), were shown to sequester PQQ in leukocytes, i.e., to form adducts with that substance. Addition of PQQ to cells blocked with the inhibitors partially restored 0°release. With respect to turning off cellular°2 release, a factor was observed to be released to the medium by old macrophages (14 days old, but not by those less than 7 days old). Such conditioned medium, when added to stimulated neutrophils or macrophages, blocked 02 release. This factor was sensitive to proteases, exhibited molecular sizes of 3 and 11 kDa, and its action was independent of the nature of the stimulus applied to the leukocytes. It was partially purified by column (sizing) chromatography and HPLC. It seems to be a general modulator of the release of reactive oxygen species by phagocytes and is irrespective of phagocytic cellular type, or species from which the cells were derived. Environ Health Perspect 102(Suppl 10): 43-44 (1994)

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“…Thus, synthetic PQQ, tritiated PQQ and DIMPDA, as well as the sizing columns and HPLC methodology used, are described (10). The cells from which the deactivating factor was obtained, the mode of harvesting, the steps of partial purification by ultrafiltration, gel filtration, and reversed-phase HPLC, etc., are described (8,11).…”

Section: Methodsmentioning

confidence: 99%

Aspects of the release of superoxide by leukocytes, and a means by which this is switched off.

Karnovsky

¹

,

Bishop

²

,

Camerero

³

et al. 1994

Environ Health Perspect

8

0

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Although great progress has been made in understanding the respiratory burst of leukocytes that produce superoxide (0-), it is possible that a component, or components, might have been overlooked. Furthermore, 0°production and its sequels, though cardinal in bactericidal action, might ultimately be damaging to the host's own cells. It is important, therefore, that a biologic mechanism exist to turn off 0°production by stimulated leukocytes. This article offers evidence that methoxatin (P00), a redox-cycling orthoquinone, might be involved in 0°production by leukocytes. This is based on the fact that inhibitors of 0°production, such as diphenylene iodonium (DPI) and 4,5-dimethylphenylene diamine (DIMPDA), were shown to sequester PQQ in leukocytes, i.e., to form adducts with that substance. Addition of PQQ to cells blocked with the inhibitors partially restored 0°release. With respect to turning off cellular°2 release, a factor was observed to be released to the medium by old macrophages (14 days old, but not by those less than 7 days old). Such conditioned medium, when added to stimulated neutrophils or macrophages, blocked 02 release. This factor was sensitive to proteases, exhibited molecular sizes of 3 and 11 kDa, and its action was independent of the nature of the stimulus applied to the leukocytes. It was partially purified by column (sizing) chromatography and HPLC. It seems to be a general modulator of the release of reactive oxygen species by phagocytes and is irrespective of phagocytic cellular type, or species from which the cells were derived. Environ Health Perspect 102(Suppl 10): 43-44 (1994)

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Leukocyte‐deactivating factor from macrophages: Partial purification and biochemical characterization. A novel cytokine

Cited by 7 publications

References 30 publications

Antinociceptive effect of the calcium-binding protein MRP-14 and the role played by neutrophils on the control of inflammatory pain

Antinociceptive effect of the calcium-binding protein MRP-14 and the role played by neutrophils on the control of inflammatory pain

Aspects of the Release of Superoxide by Leukocytes, and a Means by Which This Is Switched off

Aspects of the release of superoxide by leukocytes, and a means by which this is switched off.

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