Presence and active synthesis of the 67 kDa elastin-receptor in human circulating white blood cells

doi:10.1016/j.bbrc.2005.05.021

Biochemical and Biophysical Research Communications

Volume 332, Issue 3, 8 July 2005, Pages 787-792

https://doi.org/10.1016/j.bbrc.2005.05.021 Get rights and content

Abstract

Early after the identification of the elastin-receptor (El-R) on mesenchymal cells, it was demonstrated that phagocytic cells and lymphocytes could also respond to elastin peptides. Nevertheless, the level of El-R expression has never been demonstrated on immune cells and no data exist whether these cells actively synthesize this El-R. Thus, our aim in the present work was to study the expression and number of El-R on white blood cells (WBC) using a specific 67 kDa El-R antibody and to demonstrate the presence of mRNA corresponding to the gene coding for El-R. Our results show that messenger RNA corresponding to the presumptive gene coding for the 67 kDa El-R subunit could be detected in all three WBC-types investigated. On all of these WBC, the presence of El-R could be demonstrated, however their number and their function varied following the cell type. The presence of El-R is very important for the interaction of circulating cell with the matrix as these cells intervene during atherosclerosis and in host defence.

Section snippets

Materials and methods

White blood cells separation. Venous blood was collected from 15 healthy young subjects. All subjects gave their informed consent and the protocol was approved by the Hospital Ethical Committee. Polymorphonuclear neutrophils (PMN), monocytes, and lymphocytes (Ly) were isolated from freshly drawn human blood by sequential sedimentation on 2% Dextran T-500 (Amersham Biosciences, Baie d’Urfé, Que.) in 0.9% sodium chloride, and centrifugation on a Ficoll–Hypaque cushion (specific gravity 1.077,

Biological effects of k-elastin on neutrophils and T cells

Our previous experiments with monocytes showed that addition of k-elastin at low concentrations (1–10 μg/ml) triggered several typical reactions similar to those observed after the addition of FMLP, such as burst of lytic enzymes, reactive oxygen species production, and chemotaxis [15]. We studied here whether k-elastin could exert identical effects on neutrophils. We show here that k-elastin at 1 μg/ml concentration was able to exert a significant chemotactic effect on neutrophils (Fig. 1A with *

Discussion

It has been previously shown that elastin peptides stimulated various activities in several cell types, including the proliferation of fibroblasts, the production of superoxide anion by PMN and monocytes. We further extended these observations by demonstrating for the first time that elastin peptides are not only chemotactic for monocytes, but also for neutrophils. These biological effects of elastin peptides on phagocytic cells are of great functional importance as these cells are

Acknowledgments

This work was supported by the Grant-in-Aid of the Canadian Institute of Health Research (No. 63149) and the Research Center on Aging.

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Age-dependent changes of K-elastin stimulated effector functions of human phagocytic cells: relevance for atherogenesis
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Age-related alterations in the signal transduction pathways of elastin–laminin receptor
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The elastin peptides-mediated induction of pro-collagenase-1 production by human fibroblasts involves activation of MEK/ERK pathway via PKA- and PI(3)K-dependent signaling
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Modulation of T lymphocyte proliferation and apoptosis by oxidized low density lipoproteins: potential role in atherosclerosis
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Dehydroepiandrosterone protects low density lipoproteins against preoxidation by free radicals produced by gamma-radiolysis of ethanol–water mixtures
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Alternative splicing of beta galactosidase mRNA generates the classical lysosomal enzyme and a beta-galactosidase-related protein
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Cited by (10)

The role of elastin peptides in modulating the immune response in aging and age-related diseases
2012, Pathologie Biologie
Citation Excerpt :
Altogether, these data show a strong interaction among peripheral blood cells, the matrix protein and EPs through their surface 67 kDa elastin-laminin receptor. Moreover, these cells are able to actively synthesize this 67 kDa elastin-laminin receptor [79]. It was also shown that EPs favor the Th1 response as the typical Th1 cytokines were found increased [12].
It is now well accepted that aging is associated with the occurrence of a low-grade inflammation called Inflamm-aging. This leads to the imbalance between the various mediators of the inflammatory response in favour of the pro-inflammatory response represented by pro-inflammatory cytokines and oxidative stress. The question that arises, and is still under investigation, what is the origin of the driving force leading to these changes. One of the current hypotheses is that chronic stimulation of the immune system contributes to the pro-inflammatory shift. The chronic stimulation can be of viral origin such as cytomegalovirus, from tumor antigens or from other sources such as the extracellular matrix, especially from elastin fibres and collagens. Aging and various inflammatory diseases such as atherosclerosis, abdominal aortic aneurysms, chronic obstructive pulmonary diseases (COPD), cancer and type 2 diabetes are characterized by the destruction of elastin fibers and the consequent generation of elastin peptides which are biologically active. This review will describe the putative contribution of elastin peptides to inflamm-aging and extend on their role on immunosenescence, as well as on age-associated chronic inflammatory diseases.
Il est connu que le vieillissement est associé avec un état d’inflammation à bas bruit appelé inflamm-aging. Cela conduit à un déséquilibre entre les différents médiateurs de la réponse inflammatoire en faveur de la réponse pro-inflammatoire représentée par la présence de cytokines pro-inflammatoires et le stress oxydatif. La question qui se pose, et étant toujours sous investigation, concerne l’origine de la force motrice qui mènent à ces changements. L’hypothèse la plus acceptée actuellement est celle qui soutient qu’une stimulation antigénique chronique du système immun contribue à son changement vers un état pro-inflammatoire. Cette stimulation antigénique chronique peut être d’origine virale, incluant le cytomégalovirus, tumorale ou d’autres sources comme la matrice extracellulaire et plus spécifiquement des fibres d’élastine et de collagène. Le vieillissement et divers maladie inflammatoires associées au vieillissement comme l’athérosclérose, l’anévrisme aortique abdominal, la chronic obstructive pulmonary disease (MPOC), le cancer et diabètes mellitus de type 2 sont caractérisées par la destruction de fibres d’élastine et par la génération conséquente de peptides d’élastine qui sont biologiquement actives. Cette revue décrira la contribution putative des peptides d’élastine à inflamm-aging et étendre leur rôle à l’immunosenescence, ainsi que dans les maladies inflammatoires associées à l’âge.
Fragments of extracellular matrix as mediators of inflammation
2008, International Journal of Biochemistry and Cell Biology
Citation Excerpt :
Recent studies have shown that the Neu-1 component of the EBP complex is responsible for triggering cellular activation (Duca et al., 2007). EBP is present on many cell types, including various types of leukocytes, mesenchymal cells, vascular smooth muscle cells, and skin fibroblasts (Duca et al., 2007; Hinek, 1996; Larbi et al., 2005; Malvagia et al., 2004; Tatano et al., 2006). A single ECM component can have more than one receptor involved in stimulating chemotactic responses.
Classically, the extracellular matrix (ECM) was viewed as a supporting structure for stabilizing the location of cells in tissues and for preserving the architecture of tissues. This conception has changed dramatically over the past few decades with discoveries that ECM has profound influences on the structure, viability, and functions of cells. Much of the data supporting this new paradigm has been obtained from studies of normal and pathological structural cells such as fibroblasts, smooth muscle cells, and malignant cells, as, for example, breast cancer epithelial cells. However, there has also been recognition that effects of ECM on cells extend to inflammatory cells. In this context, attention has been drawn to fragments of ECM components. In this review, we present information supporting the concept that proteolytic fragments of ECM affect multiple functions and properties of inflammatory and immune cells. Our focus is particularly upon neutrophils, monocytes, and macrophages and fragments derived from collagens, elastin, and laminins. Hyaluronan fragments, although they are not products of proteolysis, are also discussed, as they are a notable example of ECM fragments that exhibit important effects on inflammatory cells. Further, we summarize some exciting recent developments in this field as a result of mouse models in which defined ECM fragments and their receptors are clearly implicated in inflammation in vivo. Thus, this review underscores the idea that proteolysis of ECM may well have implications that go beyond modifying the structural environment of cells and tissues.
Impairment of neutrophil reactivity to elastin peptides in COPD
2013, Thorax
Citation Excerpt :
This elastin receptor complex is also composed of two other subunits named neuraminidase and protective protein/cathepsin A.23 Since S-Gal is expressed on the surface of neutrophils24 and as EPs are largely generated during COPD, we hypothesized that the inflammatory and chemotactic properties of neutrophils may be modulated by EP/cell interactions during COPD progression, notably during the exacerbation phases associated with bacterial infection. In this study, we demonstrated that impairment of neutrophil reactivity to EPs was related to S-Gal elastin receptor downregulation in patients with COPD.
Neutrophils play an important role in the inflammatory process associated with chronic obstructive pulmonary disease (COPD). Lung-infiltrating neutrophils secrete elastinolytic proteases that participate in elastin breakdown and the formation of elastin peptides (EPs).
We hypothesized that circulating neutrophil-associated immune response may be modulated by EPs during COPD.
Neutrophils obtained from patients with either stable or exacerbated COPD and controls were cultured with or without EPs. Cell chemotaxis was analysed by the Boyden method and cytokine expression was analysed by ELISA and real-time reverse transcriptase PCR. Bacterial phagocytosis and killing of ingested bacteria were evaluated after incubation with Pseudomonas aeruginosa. Reactive oxygen species (ROS) measurement and elastin receptor expression were determined by flow cytometry.
Chemotactic activity of neutrophils from patients with COPD towards the VGVAPG EP was reduced compared with controls. VGVAPG increased proinflammatory cytokine synthesis and bacterial load, but reduced ROS production in neutrophils from controls and from patients with stable COPD. Patients with exacerbated COPD were unresponsive to VGVAPG treatment. These findings were associated with a decreased or almost complete loss of S-Gal elastin receptor expression in neutrophils from patients with stable or exacerbated COPD, respectively.
The study demonstrates that the response of neutrophils from patients with COPD to VGVAPG varied according to COPD phase and critical level of S-Gal expression. S-Gal downregulation could result from a feedback mechanism induced by high levels of EPs.
Radiation-induced graft polymerization of elastin onto polyvinylpyrrolidone as a possible wound dressing
2021, Cellular and Molecular Biology
Molecular targets and related biologic activities of fucoidan: A review
2020, Marine Drugs
Hypertrophy of the lumbar ligamentum flavum is associated with inflammation-related TGF-β expression
2011, Acta Neurochirurgica

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Biochemical and Biophysical Research Communications

Abstract

Section snippets

Materials and methods

Biological effects of k-elastin on neutrophils and T cells

Discussion

Acknowledgments

References (24)

Age-dependent changes of K-elastin stimulated effector functions of human phagocytic cells: relevance for atherogenesis

Exp. Gerontol.

Age-related alterations in the signal transduction pathways of elastin–laminin receptor

Pathol. Biol.

The elastin peptides-mediated induction of pro-collagenase-1 production by human fibroblasts involves activation of MEK/ERK pathway via PKA- and PI(3)K-dependent signaling

FEBS Lett.

Modulation of T lymphocyte proliferation and apoptosis by oxidized low density lipoproteins: potential role in atherosclerosis

Atherosclerosis

Dehydroepiandrosterone protects low density lipoproteins against preoxidation by free radicals produced by gamma-radiolysis of ethanol–water mixtures

Atherosclerosis

Alternative splicing of beta galactosidase mRNA generates the classical lysosomal enzyme and a beta-galactosidase-related protein

J. Biol. Chem.

Elastin peptides induce migration and terminal differentiation of cultured keratinocytes via 67 kDa elastin receptor in vitro: 67 kDa receptor is expressed in the kertinocytes eliminating elastic materials in elastosis perforans serpiginosa

J. Invest. Dermatol.

The intracellular status of Streptococcus pyogenes: role of extracellular matrix-binding proteins and their regulation

Int. J. Med. Microbiol.

Aging of the vascular wall and atherogenesis: role of the elastin–laminin receptor

Atherosclerosis

Effect of elastin peptides and N-formyl-methionyl-leucyl phenylalanine on cytosolic free calcium in polymorphonuclear leukocytes of healthy middle-aged and elderly subjects

Clin. Biochem.

Lymphocytes in human atherosclerotic plaque exhibit the elastin–laminin receptor: potential role in atherogenesis

Atherosclerosis

Biological roles of the non-integrin elastin/laminin receptor

Biol. Chem.

Cited by (10)

The role of elastin peptides in modulating the immune response in aging and age-related diseases

Fragments of extracellular matrix as mediators of inflammation

Impairment of neutrophil reactivity to elastin peptides in COPD

Radiation-induced graft polymerization of elastin onto polyvinylpyrrolidone as a possible wound dressing

Molecular targets and related biologic activities of fucoidan: A review

Hypertrophy of the lumbar ligamentum flavum is associated with inflammation-related TGF-β expression