Endotoxin promotes adhesion of human erythrocytes to human vascular endothelial cells under conditions of flow

Eichelbrönner, Otto; Sielenkämper, Andreas W.; Cepinskas, Gediminas; Sibbald, William J.; Chin‐Yee, Ian

doi:10.1097/00003246-200006000-00030

Cited by 63 publications

(30 citation statements)

References 25 publications

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“…The LPS-induced fall in RBC counts can probably be attributed to enhanced degradation (due to decreased deformability and increased osmotic fragility), consumption into microaggregates and reduced production (under bone marrow suppression of erythropoietin levels). 56,57 The rapid leukocyte decrease is likely due to tissue migration. 5,58 Together, these observations support the notion that AChE-R plays an active role in the proliferation of hematopoietic progenitors, especially Mks, without compromising their ability to differentiate into the various hematopoietic lineages.…”

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confidence: 99%

Stress-induced cholinergic signaling promotes inflammation-associated thrombopoiesis

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Perry

Lapidot

et al. 2006

Blood

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To study the role of the stress-induced "readthrough" acetylcholinesterase splice variant, AChE-R, in thrombopoiesis, we used transgenic mice overexpressing human AChE-R (TgR). Increased AChE hydrolytic activity in the peripheral blood of TgR mice was associated with increased thrombopoietin levels and platelet counts. Bone marrow (BM) progenitor cells from TgR mice presented an elevated capacity to produce mixed (GEMM) and megakaryocyte (Mk) colonies, which showed intensified labeling of AChE-R and its interacting proteins RACK1 and PKC. When injected with bacterial lipopolysaccharide (LPS), parent strain FVB/N mice, but not TgR mice, showed reduced platelet counts. Therefore, we primed human CD34 ؉ cells with the synthetic ARP 26 peptide, derived from the cleavable C-terminus of AChE-R prior to transplantation, into sublethally irradiated NOD/SCID mice. Engraftment of human cells (both CD45 ؉ and CD41 ؉ Mk) was significantly increased in mice that received ARP 26 IntroductionThe number of circulating blood cells is tightly regulated by cytokines and chemokines capable of immediate response to various stimuli. 1 Adjustment to changing needs involves rapid mobilization of cells from the bone marrow (BM) and the vascular marginal pool in response to inflammation, stress, or injury. 2 An example is inflammation-inducible hematopoiesis, which was thoroughly studied in murine models using bacterial lipopolysaccharide (LPS), the main cell-wall component of gram-negative bacteria. 3 LPS is an endotoxin that stimulates an acute inflammatory response via the CD14 receptor and the Toll-like receptor-4 (TLR4) found on monocytes and tissue macrophages. 4 LPS-TLR4 interaction initiates a signal transduction cascade that leads to the release of pro-inflammatory cytokines, 3 including tumor necrosis factor (TNF)-␣, interleukin (IL)-1␤, -6, and -8, and others. These cytokines activate the mobilization of hematopoietic cells from the BM 5 and set in motion the migration of leukocytes from blood vessel walls, increasing their numbers in the circulation. 6 The net result of this process is an immediate and dramatic increase in the number of circulating peripheral blood (PB) cells, needed to mount the immune response, accompanied by a corresponding decrease in BM cell numbers, which in turn induces a compensatory increase in their production. 7 Many factors are involved in abating the inflammatory response and allowing the recovery of hemostasis. Acetylcholine (ACh), one of these factors, acts by attenuating the secretion of proinflammatory cytokines at the posttranscriptional level via activation of nicotinic receptors on tissue macrophages. 8 Circulating acetylcholinesterase (AChE) controls the levels of ACh, suggesting promotion of the inflammatory process under AChE excess. 9 There are 3 C-terminally variant forms of AChE: synaptic (S), erythrocytic (E), and readthrough (R). All are ubiquitously expressed in hematopoietic cell lineages, especially in megakaryocytes (Mks) and erythrocytes. [10][11][12] Importantly, AChE contri...

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confidence: 99%

Stress-induced cholinergic signaling promotes inflammation-associated thrombopoiesis

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Perry

Lapidot

et al. 2006

Blood

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“…Although not extensively investigated, there is some evidence for this phenomenon. Incubation of both endothelial cells and RBCs with endotoxin increased adherence of RBCs to endothelial monolayers [105]. This effect was also observed after stimulation with TNF- [106].…”

Section: Reduced Deformabilitymentioning

confidence: 72%

Red Blood Cell Clearance in Inflammation

Straat

Bruggen²,

Korte³

et al. 2012

Transfus Med Hemother

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Anemia is a frequently encountered problem in the critically ill patient. The inability to compensate for anemia includes several mechanisms, collectively referred to as anemia of inflammation: reduced production of erythropoietin, impaired bone marrow response to erythropoietin, reduced iron availability, and increased red blood cell (RBC) clearance. This review focuses on mechanisms of RBC clearance during inflammation. We state that phosphatidylserine (PS) expression in inflammation is mainly enhanced due to an increase in ceramide, caused by an increase in sphingomyelinase activity due to either platelet activating factor, tumor necrosis factorα, or direct production by bacteria. Phagocytosis of RBCs during inflammation is mediated via RBC membrane protein band 3. Reduced deformability of RBCs seems an important feature in inflammation, also mediated by band 3 as well as by nitric oxide, reactive oxygen species, and sialic acid residues. Also, adherence of RBCs to the endothelium is increased during inflammation, most likely due to increased expression of endothelial adhesion molecules as well as PS on the RBC membrane, in combination with decreased capillary blood flow. Thereby, clearance of RBCs during inflammation shows similarities to clearance of senescent RBCs, but also has distinct entities, including increased adhesion to the endothelium.

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“…In a previous investigation we observed that ETX promotes adhesion of RBCs to venous endothelial cells at continuous flow [3]. However, shear forces are sometimes inconsistent and shear forces lower than those occurring with physiological venous flow are observed in near stasis conditions, such as might be found during the process of acute inflammation [32].…”

Section: Discussionmentioning

confidence: 88%

“…Reductions in the perfused capillary density, increased intermittent flow or flow stasis, and alterations in red blood cell velocity relative to normal subjects have been found after exposure to ETX or peritonitisinduced sepsis [9,11,12]. In a previous investigation we demonstrated that ETX increases RBC adhesion to endothelium in a dynamic environment generated by constant flow [3]. The accumulated evidence suggests that the various microcirculatory blood flow pattern and shear forces particularly those prevailing in splanchnic organs during systemic inflammation affect RBC-endothelial cell interactions.…”

Section: Introductionmentioning

confidence: 92%

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Intermittent flow increases endotoxin-induced adhesion of human erythrocytes to vascular endothelial cells

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Endotoxin promotes adhesion of human erythrocytes to human vascular endothelial cells under conditions of flow

Cited by 63 publications

References 25 publications

Stress-induced cholinergic signaling promotes inflammation-associated thrombopoiesis

Stress-induced cholinergic signaling promotes inflammation-associated thrombopoiesis

Red Blood Cell Clearance in Inflammation

Intermittent flow increases endotoxin-induced adhesion of human erythrocytes to vascular endothelial cells

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