ArticleAmerican journal of respiratory and critical care medicine2010
Urokinase-type plasminogen activator inhibits efferocytosis of neutrophils.
Article in American journal of respiratory and critical care medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
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- A cyclic azapeptide ligand of the scavenger receptor CD36/SR-B2 reduces the atherosclerotic lesion progression and enhances plaque stability in apolipoprotein E-deficient mice.Frontiers in pharmacology · 2023Article
- Epithelial sodium channels in macrophage migration and polarization: role of proinflammatory cytokines TNFα and IFNγ.American journal of physiology. Regulatory, integrative and comparative physiology · 2022Article
- From leukocyte recruitment to resolution of inflammation: the cardinal role of integrins.Journal of leukocyte biology · 2017Review
- 5-Aminoimidazole-4-carboxamide ribonucleoside-mediated adenosine monophosphate-activated protein kinase activation induces protective innate responses in bacterial endophthalmitis.Cellular microbiology · 2016Article
- Article
- Vitronectin inhibits efferocytosis through interactions with apoptotic cells as well as with macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Extracellular histones inhibit efferocytosis.Molecular medicine (Cambridge, Mass.) · 2012Article
- Vitronectin inhibits neutrophil apoptosis through activation of integrin-associated signaling pathways.American journal of respiratory cell and molecular biology · 2012Article
- Participation of the receptor for advanced glycation end products in efferocytosis.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- Update in acute lung injury and critical care 2010.American journal of respiratory and critical care medicine · 2011Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
rationalePhagocytosis of apoptotic cells, also called efferocytosis, plays an essential role in the resolution of inflammation. Urokinase-type plasminogen activator (uPA) is a multifunctional protein that has been implicated in inflammatory conditions, including pneumonia and severe infection, which are often accompanied by the development of acute lung injury. However, the role of uPA in modulating efferocytosis of apoptotic neutrophils has not been defined.
objectivesTo characterize the role of uPA in regulation of efferocytosis and to delineate the underlying mechanisms involved in this process.
methodsIn vitro and in vivo phagocytosis, immunoprecipitation, and Western blotting assays. MEASUREMENTS AND MAIN
resultsThe phagocytosis of apoptotic neutrophils by macrophages was significantly inhibited by uPA. Mutant uPA lacking the growth factor domain and catalytically inactive uPA had similar inhibitory effects on efferocytosis, as did wild-type uPA. In contrast, absence of the kringle domain abrogated the ability of uPA to diminish efferocytosis. Both the α(V)β₃ integrin and vitronectin seemed to be involved in the inhibition of efferocytosis by uPA. Incubation of macrophages with uPA also diminished activation of the small GTPase Rac-1, which normally occurs during ingestion of apoptotic neutrophils. Under in vivo conditions in the lungs, uPA decreased the uptake of apoptotic neutrophils by alveolar macrophages.
conclusionsOur data demonstrate a novel role for uPA in which it is able to diminish the uptake of apoptotic neutrophils by macrophages under both in vitro and in vivo conditions.
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