ArticleAmerican journal of physiology. Cell physiology2010
Receptor cleavage reduces the fluid shear response in neutrophils of the spontaneously hypertensive rat.
Article in American journal of physiology. Cell physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Innate Immune Cells and Hypertension: Neutrophils and Neutrophil Extracellular Traps (NETs).Comprehensive Physiology · 2021Review
- The Neutrophil: Constant Defender and First Responder.Frontiers in immunology · 2020Review
- Go with the flow: GEF-H1 mediated shear stress mechanotransduction in neutrophils.Small GTPases · 2020Review
- Pancreatic source of protease activity in the spontaneously hypertensive rat and its reduction during temporary food restriction.Microcirculation (New York, N.Y. : 1994) · 2019Article
- Effects of Transient Exposure to High Shear on Neutrophil Rolling Behavior.Cellular and molecular bioengineering · 2018Article
- IGF-1 receptor cleavage in hypertension.Hypertension research : official journal of the Japanese Society of Hypertension · 2018Article
- Fluid shear-induced cathepsin B release in the control of Mac1-dependent neutrophil adhesion.Journal of leukocyte biology · 2017Article
- The autodigestion hypothesis: Proteolytic receptor cleavage in rheological and cardiovascular cell dysfunction1.Biorheology · 2016Article
- Proteolytic receptor cleavage in the pathogenesis of blood rheology and co-morbidities in metabolic syndrome. Early forms of autodigestion.Biorheology · 2015Review
- Cleavage and reduced CD36 ectodomain density on heart and spleen macrophages in the spontaneously hypertensive rat.Microvascular research · 2014Article
- The autodigestion hypothesis for shock and multi-organ failure.Annals of biomedical engineering · 2014Review
- Molecular Signals Elicited by GPCR Agonists in Hypertension, Cardiovascular Remodeling: Are MMPs and ADAMs Elusive Therapeutic Targets?Current hypertension reviews · 2012Article
- Receptor cleavage and P-selectin-dependent reduction of leukocyte adhesion in the spontaneously hypertensive rat.Journal of leukocyte biology · 2012Article
- Shear-induced resistance to neutrophil activation via the formyl peptide receptor.Biophysical journal · 2012Article
- Proteolytic Activity Attenuates the Response of Endothelial Cells to Fluid Shear Stress.Cellular and molecular bioengineering · 2012Article
- An emerging role of degrading proteinases in hypertension and the metabolic syndrome: autodigestion and receptor cleavage.Current hypertension reports · 2012Review
- Article
- Proteolytic Cleavage of the Red Blood Cell Glycocalyx in a Genetic Form of Hypertension.Cellular and molecular bioengineering · 2011Article
- Membrane cholesterol modulates the fluid shear stress response of polymorphonuclear leukocytes via its effects on membrane fluidity.American journal of physiology. Cell physiology · 2011Article
- Matrix metalloproteinase activity causes VEGFR-2 cleavage and microvascular rarefaction in rat mesentery.Microcirculation (New York, N.Y. : 1994) · 2011Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Physiological fluid shear stress evokes pseudopod retraction in normal leukocytes by a mechanism that involves the formyl peptide receptor (FPR) as mechanosensor. In hypertensives, such as the spontaneously hypertensive rat (SHR), leukocytes lack the normal fluid shear response. The increased activity of matrix metalloproteinases (MMPs, including MMP-9) in SHR plasma is associated with cleavage of several cell membrane receptors. We hypothesize that the attenuated fluid shear response in leukocytes (neutrophils) of the SHR is due to extracellular proteolytic cleavage of the FPR. We show that suspended SHR neutrophils in whole blood sheared in a cone-and-plate device or individual neutrophils adherent to a glass surface and subject to fluid shear exhibited reduced pseudopod retractions compared with neutrophils of control Wistar-Kyoto (WKY) rats. SHR neutrophils and naïve Wistar rat neutrophils exposed to SHR plasma also exhibited impaired fluid shear responses as shown by their inability to project pseudopods with fluid shear. Labeling of extracellular FPR revealed that the FPR density in SHR neutrophils is on average 27% reduced compared with those of the WKY rats. Exposure of Wistar rat neutrophils to the gelatinase MMP-9 (final concentration 5 nM) led to attenuation of fluid shear response and decrease in extracellular FPR density. Chronic treatment of the SHR with a broad-acting MMP inhibitor, doxycycline, significantly improved the fluid shear response and increased the FPR extracellular density of SHR neutrophils. These results suggest that proteolytic cleavage of the FPR may interfere with normal fluid shear-induced pseudopod retractions in SHR neutrophils.
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Registered trials
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