scholarly journals Hyaluronan as an Immune Regulator in Human Diseases

2011 ◽  
Vol 91 (1) ◽  
pp. 221-264 ◽  
Author(s):  
Dianhua Jiang ◽  
Jiurong Liang ◽  
Paul W. Noble
Keyword(s):  
Cell Surface ◽  
Tissue Injury ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Surface Proteins ◽  
Human Diseases ◽  
Inflammatory Genes ◽  
Extracellular Matrix Components ◽  
Injury And Repair

Accumulation and turnover of extracellular matrix components are the hallmarks of tissue injury. Fragmented hyaluronan stimulates the expression of inflammatory genes by a variety of immune cells at the injury site. Hyaluronan binds to a number of cell surface proteins on various cell types. Hyaluronan fragments signal through both Toll-like receptor (TLR) 4 and TLR2 as well as CD44 to stimulate inflammatory genes in inflammatory cells. Hyaluronan is also present on the cell surface of epithelial cells and provides protection against tissue damage from the environment by interacting with TLR2 and TLR4. Hyaluronan and hyaluronan-binding proteins regulate inflammation, tissue injury, and repair through regulating inflammatory cell recruitment, release of inflammatory cytokines, and cell migration. This review focuses on the role of hyaluronan as an immune regulator in human diseases.

Immune Mechanisms and Related Targets for the Treatment of Fibrosis in Various Organs

2022 ◽  
Vol 22 ◽  
Author(s):  
Anita A Pinar ◽  
Chrishan S S Samuel
Keyword(s):  
Tissue Injury ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Specific Cell ◽  
Fibrotic Response ◽  
Immune Mechanisms ◽  
Emerging Therapies ◽  
Fibrotic Process ◽  
Antigen Presenting

Abstract: Inflammation and fibrosis are two inter‐related disease pathologies with several overlapping components. Three specific cell types, macrophages, T helper cells and myofibroblasts, each play important roles in regulating both processes. Following tissue injury, an inflammatory stimulus is often necessary to initiate tissue repair, where cytokines released from infiltrating and resident immune and inflammatory cells stimulate the proliferation and activation of extracellular matrix-producing myofibroblasts. However, persistent tissue injury drives an inappropriate pro‐fibrotic response. Additionally, activated myofibroblasts can take on the role of traditional antigen-presenting cells, secrete pro‐inflammatory cytokines, and recruit inflammatory cells to fibrotic foci, amplifying the fibrotic response in a vicious cycle. Moreover, inflammatory cells have been shown to play contradictory roles in the initiation, amplification and resolution of fibrotic disease processes. The central role of the inflammasome molecular platform in contributing to fibrosis is only beginning to be fully appreciated. In this review, we discuss the immune mechanisms that can lead to fibrosis, the inflammasomes that have been implicated in the fibrotic process in the context of the immune response to injury, and also discuss current and emerging therapies that target inflammasome-induced collagen deposition to treat organ fibrosis.

Ecto-ADP-ribose Transferases: Cell-Surface Response to Local Tissue Injury

Physiology ◽  
2005 ◽  
Vol 20 (6) ◽  
pp. 374-381 ◽  
Author(s):  
Anna Zolkiewska
Keyword(s):  
Cell Surface ◽  
Tissue Injury ◽  
Membrane Receptors ◽  
Surface Proteins ◽  
Main Role ◽  
Membrane Stress ◽  
Cell Surface Proteins ◽  
Physiological Conditions ◽  
Arginine Residues

Ecto-ADP-ribose transferases (ecto-ARTs) catalyze the transfer of ADP-ribose from NAD+ to arginine residues in cell-surface proteins. Since the concentration of extracellular NAD+ is very low under normal physiological conditions but rises significantly upon tissue injury or membrane stress, it is postulated that the main role of ecto-ARTs is to ADP-ribosylate and regulate the function of certain membrane receptors in response to elevated levels of NAD+.

scholarly journals Syndecans and Pancreatic Ductal Adenocarcinoma

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 349
Author(s):  
Nausika Betriu ◽  
Juan Bertran-Mas ◽  
Anna Andreeva ◽  
Carlos E. Semino
Keyword(s):  
Extracellular Matrix ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cell Types ◽  
Ductal Adenocarcinoma ◽  
Physiological Processes ◽  
Extracellular Matrix Components ◽  
Detection And Diagnosis ◽  
And Migration ◽  
Early Detection And Diagnosis

Pancreatic Ductal Adenocarcinoma (PDAC) is a fatal disease with poor prognosis because patients rarely express symptoms in initial stages, which prevents early detection and diagnosis. Syndecans, a subfamily of proteoglycans, are involved in many physiological processes including cell proliferation, adhesion, and migration. Syndecans are physiologically found in many cell types and their interactions with other macromolecules enhance many pathways. In particular, extracellular matrix components, growth factors, and integrins collect the majority of syndecans associations acting as biochemical, physical, and mechanical transducers. Syndecans are transmembrane glycoproteins, but occasionally their extracellular domain can be released from the cell surface by the action of matrix metalloproteinases, converting them into soluble molecules that are capable of binding distant molecules such as extracellular matrix (ECM) components, growth factor receptors, and integrins from other cells. In this review, we explore the role of syndecans in tumorigenesis as well as their potential as therapeutic targets. Finally, this work reviews the contribution of syndecan-1 and syndecan-2 in PDAC progression and illustrates its potential to be targeted in future treatments for this devastating disease.

Role of cations in the flocculation of Saccharomyces cerevisiae and discrimination of the corresponding proteins

1991 ◽  
Vol 37 (5) ◽  
pp. 397-403 ◽  
Author(s):  
Hiroshi Kuriyama ◽  
Itaru Umeda ◽  
Harumi Kobayashi
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Surface ◽  
Inhibitory Effect ◽  
Surface Proteins ◽  
Promoting Effect ◽  
Yeast Strains ◽  
Yeast Flocculation ◽  
Different Types ◽  
Anionic Groups

Asexual yeast flocculation was studied using strong flocculents of Saccharomyces cerevisiae. The inhibitory effect of cations on flocculation is considered to be caused by competition between those cations and Ca2+ at the binding site of the Ca2+-requiring protein that is involved in flocculation. Inhibition of flocculation by various cations occurred in the following order: La3+, Sr2+, Ba2+, Mn2+, Al3+, and Na+. Cations such as Mg2+, Co2+, and K+ promoted flocculation. This promoting effect may be based on the reduction of electrostatic repulsive force between cells caused by binding of these cations anionic groups present on the cell surface. In flocculation induced by these cations, trace amounts of Ca2+ excreted on the cell surface may activate the corresponding protein. The ratio of Sr2+/Ca2+ below which cells flocculated varied among strains: for strains having the FLO5 gene, it was 400 to 500; for strains having the FLO1 gene, about 150; and for two alcohol yeast strains, 40 to 50. This suggests that there are several different types of cell surface proteins involved in flocculation in different yeast strains. Key words: yeast, flocculation, protein, cation, calcium.

scholarly journals Lactobacillus Cell Surface Proteins Involved in Interaction with Mucus and Extracellular Matrix Components

2020 ◽  
Vol 77 (12) ◽  
pp. 3831-3841
Author(s):  
Lidia Muscariello ◽  
Barbara De Siena ◽  
Rosangela Marasco
Keyword(s):  
Extracellular Matrix ◽  
Cell Surface ◽  
Intestinal Flora ◽  
Surface Proteins ◽  
Matrix Proteins ◽  
Cell Surface Proteins ◽  
Host Interaction ◽  
Extracellular Matrix Components ◽  
Probiotic Strains ◽  
Matrix Components

AbstractThe gut microbiota is a complex microbial ecosystem where bacteria, through mutual interactions, cooperate in maintaining of wellbeing and health. Lactobacilli are among the most important constituents of human and animal intestinal microbiota and include many probiotic strains. Their presence ensures protection from invasion of pathogens, as well as stimulation of the immune system and protection of the intestinal flora, often exerted through the ability to interact with mucus and extracellular matrix components. The main factors responsible for mediating adhesion of pathogens and commensals to the gut are cell surface proteins that recognize host targets, as mucus layer and extracellular matrix proteins. In the last years, several adhesins have been reported to be involved in lactobacilli–host interaction often miming the same mechanism used by pathogens.

scholarly journals Interaction of single-chain urokinase with its receptor induces the appearance and disappearance of binding epitopes within the resultant complex for other cell surface proteins

Blood ◽  
1996 ◽  
Vol 88 (2) ◽  
pp. 542-551 ◽  
Author(s):  
AA Higazi ◽  
RH Upson ◽  
RL Cohen ◽  
J Manuppello ◽  
J Bognacki ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Surface ◽  
Binding Sites ◽  
Ldl Receptor ◽  
Cell Types ◽  
Surface Proteins ◽  
Single Chain ◽  
Cell Surface Proteins ◽  
Functional Changes ◽  
And Migration

Binding of urokinase-type plasminogen activator (uPA) to its glycosylphosphatidylinositol-anchored receptor (uPAR) initiates signal transduction, adhesion, and migration in certain cell types. To determine whether some of these activities may be mediated by associations between the uPA/uPAR complex and other cell surface proteins, we studied the binding of complexes composed of recombinant, soluble uPA receptor (suPAR) and single chain uPA (scuPA) to a cell line (LM-TK- fibroblasts) that does not express glycosylphosphatidylinositol (GPI)-anchored proteins to eliminate potential competition by endogenous uPA receptors. scuPA induced the binding of suPAR to LM-TK- cells. Binding of labeled suPAR/scuPA was inhibited by unlabeled complex, but not by scuPA or suPAR added separately, indicating cellular binding sites had been formed that are not present in either component. Binding of the complex was inhibited by low molecular weight uPA (LMW-uPA) indicating exposure of an epitope found normally in the isolated B chain of two chain uPA (tcuPA), but hidden in soluble scuPA. Binding of LMW-uPA was independent of its catalytic site and was associated with retention of its enzymatic activity. Additional cell binding epitopes were generated within suPAR itself by the aminoterminal fragment of scuPA, which itself does not bind to LM-TK- cells. When scuPA bound to suPAR, a binding site for alpha 2-macroglobulin receptor/LDL receptor-related protein (alpha 2 MR/LRP) was lost, while binding sites for cell-associated vitronectin and thrombospondin were induced. In accord with this, the internalization and degradation of cell-associated tcuPA and tcuPA-PAI- 1 complexes proceeded less efficiently in the presence of suPAR. Further, little degradation of suPAR was detected, suggesting that cell- bound complex dissociated during the initial stages of endocytosis. Thus, the interaction of scuPA with its receptor causes multiple functional changes within the complex including the dis-appearance of an epitope in scuPA involved in its clearance from the cell surface and the generation of novel epitopes that promote its binding to proteins involved in cell adhesion and signal transduction.

scholarly journals The Role of Macrophages in Vascular Repair and Regeneration after Ischemic Injury

2020 ◽  
Vol 21 (17) ◽  
pp. 6328
Author(s):  
Huiling Hong ◽  
Xiao Yu Tian
Keyword(s):  
Tissue Injury ◽  
Direct Interaction ◽  
Cell Types ◽  
Short Review ◽  
Potential Interaction ◽  
Hindlimb Ischemia ◽  
Vascular Repair ◽  
Injury Repair ◽  
Vascular Beds

Macrophage is one of the important players in immune response which perform many different functions during tissue injury, repair, and regeneration. Studies using animal models of cardiovascular diseases have provided a clear picture describing the effect of macrophages and their phenotype during injury and regeneration of various vascular beds. Many data have been generated to demonstrate that macrophages secrete many important factors including cytokines and growth factors to regulate angiogenesis and arteriogenesis, acting directly or indirectly on the vascular cells. Different subsets of macrophages may participate at different stages of vascular repair. Recent findings also suggest a direct interaction between macrophages and other cell types during the generation and repair of vasculature. In this short review, we focused our discussion on how macrophages adapt to the surrounding microenvironment and their potential interaction with other cells, in the context of vascular repair supported by evidences mostly from studies using hindlimb ischemia as a model for studying post-ischemic vascular repair.

scholarly journals Innate Immunity Effector Cells as Inflammatory Drivers of Cardiac Fibrosis

2020 ◽  
Vol 21 (19) ◽  
pp. 7165 ◽  
Author(s):  
Denisa Baci ◽  
Annalisa Bosi ◽  
Luca Parisi ◽  
Giuseppe Buono ◽  
Lorenzo Mortara ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immune Cells ◽  
Cardiac Fibrosis ◽  
Immune Cell ◽  
Tissue Injury ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Sterile Inflammation ◽  
Therapeutic Interventions ◽  
Ecm Remodeling

Despite relevant advances made in therapies for cardiovascular diseases (CVDs), they still represent the first cause of death worldwide. Cardiac fibrosis and excessive extracellular matrix (ECM) remodeling are common end-organ features in diseased hearts, leading to tissue stiffness, impaired myocardial functional, and progression to heart failure. Although fibrosis has been largely recognized to accompany and complicate various CVDs, events and mechanisms driving and governing fibrosis are still not entirely elucidated, and clinical interventions targeting cardiac fibrosis are not yet available. Immune cell types, both from innate and adaptive immunity, are involved not just in the classical response to pathogens, but they take an active part in “sterile” inflammation, in response to ischemia and other forms of injury. In this context, different cell types infiltrate the injured heart and release distinct pro-inflammatory cytokines that initiate the fibrotic response by triggering myofibroblast activation. The complex interplay between immune cells, fibroblasts, and other non-immune/host-derived cells is now considered as the major driving force of cardiac fibrosis. Here, we review and discuss the contribution of inflammatory cells of innate immunity, including neutrophils, macrophages, natural killer cells, eosinophils and mast cells, in modulating the myocardial microenvironment, by orchestrating the fibrogenic process in response to tissue injury. A better understanding of the time frame, sequences of events during immune cells infiltration, and their action in the injured inflammatory heart environment, may provide a rationale to design new and more efficacious therapeutic interventions to reduce cardiac fibrosis.

scholarly journals Posttranslational Modifications Required for Cell Surface Localization and Function of the Fungal Adhesin Aga1p

2003 ◽  
Vol 2 (5) ◽  
pp. 1099-1114 ◽  
Author(s):  
Guohong Huang ◽  
Mingliang Zhang ◽  
Scott E. Erdman
Keyword(s):  
Cell Wall ◽  
Cell Surface ◽  
Posttranslational Modifications ◽  
Transmembrane Domain ◽  
Signal Sequence ◽  
Cell Types ◽  
Fungal Species ◽  
Surface Proteins ◽  
Functional Requirements

ABSTRACT Adherence of fungal cells to host substrates and each other affects their access to nutrients, sexual conjugation, and survival in hosts. Adhesins are cell surface proteins that mediate these different cell adhesion interactions. In this study, we examine the in vivo functional requirements for specific posttranslational modifications to these proteins, including glycophosphatidylinositol (GPI) anchor addition and O-linked glycosylation. The processing of some fungal GPI anchors, creating links to cell wall β-1,6 glucans, is postulated to facilitate postsecretory traffic of proteins to cell wall domains conducive to their functions. By studying the yeast sexual adhesin subunit Aga1p, we found that deletion of its signal sequence for GPI addition eliminated its activity, while deletions of different internal domains had various effects on function. Substitution of the Aga1p GPI signal domain with those of other GPI-anchored proteins, a single transmembrane domain, or a cysteine capable of forming a disulfide all produced functional adhesins. A portion of the cellular pool of Aga1p was determined to be cell wall resident. Aga1p and the α-agglutinin Agα1p were shown to be under glycosylated in cells lacking the protein mannosyltransferase genes PMT1 and PMT2, with phenotypes manifested only in MATα cells for single mutants but in both cell types when both genes are absent. We conclude that posttranslational modifications to Aga1p are necessary for its biogenesis and activity. Our studies also suggest that in addition to GPI-glucan linkages, other cell surface anchorage mechanisms, such as transmembrane domains or disulfides, may be employed by fungal species to localize adhesins.

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