Regulation of 5-lipoxygenase activity in mononuclear phagocytes: Characterization of an endogenous cytosolic inhibitor

Michael J. Coffey; Steven E. Wilcoxen; Peter H. Sporn; Marc Peters-Golden

doi:10.1016/S0090-6980(98)00046-X

Regulation of 5-lipoxygenase activity in mononuclear phagocytes: Characterization of an endogenous cytosolic inhibitor

Michael J. Coffey^*, Steven E. Wilcoxen, Peter H. Sporn, Marc Peters-Golden

^*Corresponding author for this work

Medicine, Pulmonary Division

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

The proinflammatory leukotrienes (LT) play important roles in host defense and disease states. However, no endogenous mechanisms to downregulate 5-lipoxygenase (5-LO), the enzyme catalyzing LT synthesis, have been described. We observed that the cytosolic fraction of rat alveolar macrophages (AMs) and peritoneal macrophages (PMs), and of peripheral blood monocytes (PBMs) contain substantial amounts of 5-LO protein, but little detectable 5-LO activity. We therefore examined these mononuclear phagocyte (MNP) cytosolic fractions for inhibitory activity against 5-LO. MNP cytosol dose-dependently reduced the 5-LO activity in neutrophil (PMN) cytosol and AM membrane. Furthermore, MNP cytosol dose-dependently prolonged the lag phase of soybean lipoxygenase (LO) without affecting the rate of product formation. This effect was overcome by subsequent addition of 13(S)-hydroperoxy-9-cis- 11-trans-octadecadienoic acid (13-HpOD), suggesting that the active factor scavenges hydroperoxides. Inactivation by boiling and proteinase K suggest that is a protein. We speculate that this cytosolic factor(s) may serve as an endogenous means for the down-regulation of 5-LO in macrophages.

Original language	English (US)
Pages (from-to)	103-117
Number of pages	15
Journal	Prostaglandins and Other Lipid Mediators
Volume	56
Issue number	2-3
DOIs	https://doi.org/10.1016/S0090-6980(98)00046-X
State	Published - Jun 1998

Funding

This work was supported by a grant from the American Lung Association of Michigan. M.J.C. is the recipient of National Institutes of Health Clinical Investigator Development Award. M.P.-G. was supported by the NIH (R01-HL471), and a Career Investigator Award from the American Lung Association.

Keywords

Eicosanoid
Leukotriene
Lung
Macrophage
Monocyte

ASJC Scopus subject areas

Biochemistry
Physiology
Pharmacology
Cell Biology

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10.1016/S0090-6980(98)00046-X

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title = "Regulation of 5-lipoxygenase activity in mononuclear phagocytes: Characterization of an endogenous cytosolic inhibitor",

abstract = "The proinflammatory leukotrienes (LT) play important roles in host defense and disease states. However, no endogenous mechanisms to downregulate 5-lipoxygenase (5-LO), the enzyme catalyzing LT synthesis, have been described. We observed that the cytosolic fraction of rat alveolar macrophages (AMs) and peritoneal macrophages (PMs), and of peripheral blood monocytes (PBMs) contain substantial amounts of 5-LO protein, but little detectable 5-LO activity. We therefore examined these mononuclear phagocyte (MNP) cytosolic fractions for inhibitory activity against 5-LO. MNP cytosol dose-dependently reduced the 5-LO activity in neutrophil (PMN) cytosol and AM membrane. Furthermore, MNP cytosol dose-dependently prolonged the lag phase of soybean lipoxygenase (LO) without affecting the rate of product formation. This effect was overcome by subsequent addition of 13(S)-hydroperoxy-9-cis- 11-trans-octadecadienoic acid (13-HpOD), suggesting that the active factor scavenges hydroperoxides. Inactivation by boiling and proteinase K suggest that is a protein. We speculate that this cytosolic factor(s) may serve as an endogenous means for the down-regulation of 5-LO in macrophages.",

keywords = "Eicosanoid, Leukotriene, Lung, Macrophage, Monocyte",

author = "Coffey, {Michael J.} and Wilcoxen, {Steven E.} and Sporn, {Peter H.} and Marc Peters-Golden",

note = "Funding Information: This work was supported by a grant from the American Lung Association of Michigan. M.J.C. is the recipient of National Institutes of Health Clinical Investigator Development Award. M.P.-G. was supported by the NIH (R01-HL471), and a Career Investigator Award from the American Lung Association. ",

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T2 - Characterization of an endogenous cytosolic inhibitor

AU - Coffey, Michael J.

AU - Wilcoxen, Steven E.

AU - Sporn, Peter H.

AU - Peters-Golden, Marc

N1 - Funding Information: This work was supported by a grant from the American Lung Association of Michigan. M.J.C. is the recipient of National Institutes of Health Clinical Investigator Development Award. M.P.-G. was supported by the NIH (R01-HL471), and a Career Investigator Award from the American Lung Association.

PY - 1998/6

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N2 - The proinflammatory leukotrienes (LT) play important roles in host defense and disease states. However, no endogenous mechanisms to downregulate 5-lipoxygenase (5-LO), the enzyme catalyzing LT synthesis, have been described. We observed that the cytosolic fraction of rat alveolar macrophages (AMs) and peritoneal macrophages (PMs), and of peripheral blood monocytes (PBMs) contain substantial amounts of 5-LO protein, but little detectable 5-LO activity. We therefore examined these mononuclear phagocyte (MNP) cytosolic fractions for inhibitory activity against 5-LO. MNP cytosol dose-dependently reduced the 5-LO activity in neutrophil (PMN) cytosol and AM membrane. Furthermore, MNP cytosol dose-dependently prolonged the lag phase of soybean lipoxygenase (LO) without affecting the rate of product formation. This effect was overcome by subsequent addition of 13(S)-hydroperoxy-9-cis- 11-trans-octadecadienoic acid (13-HpOD), suggesting that the active factor scavenges hydroperoxides. Inactivation by boiling and proteinase K suggest that is a protein. We speculate that this cytosolic factor(s) may serve as an endogenous means for the down-regulation of 5-LO in macrophages.

AB - The proinflammatory leukotrienes (LT) play important roles in host defense and disease states. However, no endogenous mechanisms to downregulate 5-lipoxygenase (5-LO), the enzyme catalyzing LT synthesis, have been described. We observed that the cytosolic fraction of rat alveolar macrophages (AMs) and peritoneal macrophages (PMs), and of peripheral blood monocytes (PBMs) contain substantial amounts of 5-LO protein, but little detectable 5-LO activity. We therefore examined these mononuclear phagocyte (MNP) cytosolic fractions for inhibitory activity against 5-LO. MNP cytosol dose-dependently reduced the 5-LO activity in neutrophil (PMN) cytosol and AM membrane. Furthermore, MNP cytosol dose-dependently prolonged the lag phase of soybean lipoxygenase (LO) without affecting the rate of product formation. This effect was overcome by subsequent addition of 13(S)-hydroperoxy-9-cis- 11-trans-octadecadienoic acid (13-HpOD), suggesting that the active factor scavenges hydroperoxides. Inactivation by boiling and proteinase K suggest that is a protein. We speculate that this cytosolic factor(s) may serve as an endogenous means for the down-regulation of 5-LO in macrophages.

KW - Eicosanoid

KW - Leukotriene

KW - Lung

KW - Macrophage

KW - Monocyte

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ER -

Regulation of 5-lipoxygenase activity in mononuclear phagocytes: Characterization of an endogenous cytosolic inhibitor

Abstract

Funding

Keywords

ASJC Scopus subject areas

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