Mechanisms of leukocyte activation in the circulation

Schmid‐Schönbein, Geert W.; Zweifach, Benjamin W.; Moazzam, Fariborz

doi:10.1016/s0021-9150(97)06120-0

Cited by 4 publications

(3 citation statements)

References 13 publications

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“…Student's t-test for comparison within each group between t ϭ 0 and t ϭ 1 min: €P Ͻ 0.01, Wistar rat neutrophils in fMLP. lower deformability and in SHR capillaries cause a substantial increase in microvascular flow resistance due to hemodynamic interactions with erythrocytes (9,31).…”

Section: Discussionmentioning

confidence: 99%

Receptor cleavage reduces the fluid shear response in neutrophils of the spontaneously hypertensive rat

Chen

DeLano

Valdez

et al. 2010

American Journal of Physiology-Cell Physiology

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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.formyl peptide receptor; pseudopod projection; cone-and-plate device; N-formyl-methionine-leucine-phenylalanine; immunohistochemistry ONE OF THE FEATURES OF LEUKOCYTE stimulation by N-formylMet-Leu-Phe (fMLP) is the projection of pseudopods by Factin polymerization (8,41). In a normal circulation, the majority of leukocytes have few or no pseudopods, an effect mediated by fluid shear stress with retraction of pseudopods (14,26). However, an increased number of circulating leukocytes project pseudopods in the circulation of hypertensives, such as the spontaneously hypertensive rat (SHR), with elevated microvascular resistance (9). The impaired movement of such neutrophils with pseudopods through capillaries causes substantial elevation of hemodynamic resistance in the SHR (9). Currently, the mechanism by which an increased number of pseudopods form on circulating neutrophils of the SHR under normal physiological fluid shear is unexplored.Recently, G protein-coupled receptors, such as the formyl peptide receptor (FPR) in the case of neutrophils, have been shown to serve as mechanosensors for fluid shear stress (21). Exhibiting high constitutive activity, the FPR binding target for N-formyl chemoattractants is predominantly expressed on neutrophils and monocytes (15, 21). Herein we are interested in investigating the fluid shear response of neutrophils of ...

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Section: Discussionmentioning

confidence: 99%

Receptor cleavage reduces the fluid shear response in neutrophils of the spontaneously hypertensive rat

Chen

DeLano

Valdez

et al. 2010

American Journal of Physiology-Cell Physiology

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“…The microcirculation is one of the first targets affected by activated leukocytes and endothelial cells, resulting in tissue injury followed by peripheral hypoperfusion, hypoxia, or ischemia. [25][26][27] The muscle microcirculation with the highest capillary density is affected by leukocyte and endothelial cell activation. 12 Endothelial cells are known to produce cytokines and adhesion molecules and promote inflammation.…”

Section: Commentmentioning

confidence: 99%

Improvement in Early Symptoms of Shock by Delayed Intestinal Protease Inhibition

Fitzal

DeLano²,

Young³

et al. 2004

Arch Surg

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“…Известно, что моноцитарная окись азота является продуктом индуцируемой NO-синтазы [7]. Экспрессия гена, ответственного за синтез данного фермента, происходит в процессе активации клетки под влиянием различных стимулов (эндотоксины, IL-1, фактор некроза опухоли, межклеточные контакты, модифицированные липопротеины, напряжение сдвига) [17,25]. При этом окись азота выделяется моноцитами в течение нескольких часов и дней в концентрациях значительно больших, чем продуцируют это же вещество эндотелиальные клетки при участии конститутивной NO-синтазы [7].…”

Section: бюллетень сибирской медицины ¹ 1 2002 49unclassified

The factors of risk of the development of endothelium dysfunction that people with hereditary atherosclerosis and coronary atherosclerosis have

Ковалев¹,

Марцинкевич²,

Суслова³

et al. 2002

Bûll. sib. med.

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The research is devoted to the evaluation of the depressor and constrictive components of the vascular reactiveness in the people with burdened heredity on atherosclerosis and the factors of risk of this disease’s development. The connection of the vascular reactiveness of peripheral arteries with the factors of risk of atherosclerosis development is discovered. The results of researches allow to suppose that atherogenic factions of lipoproteins, inflammatory cytokines produced by mononuclear of nitric oxide participate in the formation of pathological vascular reactions in people with atherosclerosis and with burdened atherosclerosis heredity on preclinical disease level.

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Mechanisms of leukocyte activation in the circulation

Cited by 4 publications

References 13 publications

Receptor cleavage reduces the fluid shear response in neutrophils of the spontaneously hypertensive rat

Receptor cleavage reduces the fluid shear response in neutrophils of the spontaneously hypertensive rat

Improvement in Early Symptoms of Shock by Delayed Intestinal Protease Inhibition

The factors of risk of the development of endothelium dysfunction that people with hereditary atherosclerosis and coronary atherosclerosis have

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