A neutrophil-centric view of chemotaxis

Abstract Neutrophils are key players of the innate immune system, that are involved in coordinating the initiation, propagation and resolution of inflammation. Accurate neutrophil migration (chemotaxis) to sites of inflammation in response to gradients of chemoattractants is pivotal to these roles. Binding of chemoattractants to dedicated G-protein-coupled receptors (GPCRs) initiates downstream signalling events that promote neutrophil polarisation, a prerequisite for directional migration. We provide a brief summary of some of the recent insights into signalling events and feedback loops that serve to initiate and maintain neutrophil polarisation. This is followed by a discussion of recent developments in the understanding of in vivo neutrophil chemotaxis, a process that is frequently referred to as ‘recruitment’ or ‘trafficking’. Here, we summarise neutrophil mobilisation from and homing to the bone marrow, and briefly discuss the role of glucosaminoglycan-immobilised chemoattractants and their corresponding receptors in the regulation of neutrophil extravasation and neutrophil swarming. We furthermore touch on some of the most recent insights into the roles of atypical chemokine receptors (ACKRs) in neutrophil recruitment, and discuss neutrophil reverse (transendothelial) migration together with potential function(s) in the dissemination and/or resolution of inflammation.

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Role of Taste Receptors as Sentinels of Innate Immunity in the Upper Airway

Journal of Pathogens ◽

10.1155/2018/9541987 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 8

Author(s):

Neil N. Patel ◽

Alan D. Workman ◽

Noam A. Cohen

Keyword(s):

Airway Epithelium ◽

Taste Receptor ◽

Upper Airway ◽

Airway Disease ◽

G Protein Coupled Receptors ◽

Innate Immune ◽

Taste Receptors ◽

Taste Sensation ◽

G Protein Coupled

Evidence is emerging that shows taste receptors serve functions outside of taste sensation of the tongue. Taste receptors have been found in tissue across the human body, including the gastrointestinal tract, bladder, brain, and airway. These extraoral taste receptors appear to be important in modulating the innate immune response through detection of pathogens. This review discusses taste receptor signaling, focusing on the G-protein–coupled receptors that detect bitter and sweet compounds in the upper airway epithelium. Emphasis is given to recent studies which link the physiology of sinonasal taste receptors to clinical manifestation of upper airway disease.

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Atypical Chemokine Receptors in Cardiovascular Disease

Thrombosis and Haemostasis ◽

10.1055/s-0038-1676988 ◽

2019 ◽

Vol 119 (04) ◽

pp. 534-541 ◽

Cited By ~ 4

Author(s):

Selin Gencer ◽

Emiel van der Vorst ◽

Maria Aslani ◽

Christian Weber ◽

Yvonne Döring ◽

...

Keyword(s):

G Protein ◽

Chemokine Receptors ◽

Cellular Response ◽

Current Knowledge ◽

G Protein Coupled Receptors ◽

Signalling Pathways ◽

Atherosclerosis Development ◽

G Protein Coupled ◽

Precise Role

AbstractInflammation has been well recognized as one of the main drivers of atherosclerosis development and therefore cardiovascular diseases (CVDs). It has been shown that several chemokines, small 8 to 12 kDa cytokines with chemotactic properties, play a crucial role in the pathophysiology of atherosclerosis. Chemokines classically mediate their effects by binding to G-protein-coupled receptors called chemokine receptors. In addition, chemokines can also bind to atypical chemokine receptors (ACKRs). ACKRs fail to induce G-protein-dependent signalling pathways and thus subsequent cellular response, but instead are able to internalize, scavenge or transport chemokines. In this review, we will give an overview of the current knowledge about the involvement of ACKR1–4 in CVDs and especially in atherosclerosis development. In the recent years, several studies have highlighted the importance of ACKRs in CVDs, although there are still several controversies and unexplored aspects that have to be further elucidated. A better understanding of the precise role of these atypical receptors may pave the way towards novel and improved therapeutic strategies.

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Towards in vivo imaging of functionally active 5-HT1A receptors in schizophrenia: concepts and challenges

Translational Psychiatry ◽

10.1038/s41398-020-01119-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Oriane Razakarivony ◽

Adrian Newman-Tancredi ◽

Luc Zimmer

Keyword(s):

Psychiatric Disorders ◽

Cognitive Processes ◽

G Protein Coupled Receptors ◽

Research Paradigms ◽

New Research ◽

New Generation ◽

G Protein Coupled

AbstractThe serotonin 5-HT1A receptor has attracted wide attention as a target for treatment of psychiatric disorders. Although this receptor is important in the pharmacological mechanisms of action of new-generation antipsychotics, its characterization remains incomplete. Studies based on in vitro molecular imaging on brain tissue by autoradiography, and more recently in vivo PET imaging, have not yielded clear results, in particular due to the limitations of current 5-HT1A radiotracers, which lack specificity and/or bind to all 5-HT1A receptors, regardless of their functional status. The new concept of PET neuroimaging of functionally active G-protein-coupled receptors makes it possible to revisit PET brain exploration by enabling new research paradigms. For the 5-HT1A receptor it is now possible to use [18F]-F13640, a 5-HT1A receptor radioligand with high efficacy agonist properties, to specifically visualize and quantify functionally active receptors, and to relate this information to subjects’ pathophysiological or pharmacological state. We therefore propose imaging protocols to follow changes in the pattern of functional 5-HT1A receptors in relation to mood deficits or cognitive processes. This could allow improved discrimination of different schizophrenia phenotypes and greater understanding of the basis of therapeutic responses to antipsychotic drugs. Finally, as well as targeting functionally active receptors to gain insights into the role of 5-HT1A receptors, the concept can also be extended to the study of other receptors involved in the pathophysiology or therapy of psychiatric disorders.

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The Role of Leukotrienes as Potential Therapeutic Targets in Allergic Disorders

International Journal of Molecular Sciences ◽

10.3390/ijms20143580 ◽

2019 ◽

Vol 20 (14) ◽

pp. 3580 ◽

Cited By ~ 13

Author(s):

Airi Jo-Watanabe ◽

Toshiaki Okuno ◽

Takehiko Yokomizo

Keyword(s):

Biological Effects ◽

Expression Patterns ◽

Allergic Diseases ◽

G Protein Coupled Receptors ◽

Receptor Subtype ◽

Recent Developments ◽

Acute And Chronic Inflammation ◽

Allergic Disorders ◽

G Protein Coupled

Leukotrienes (LTs) are lipid mediators that play pivotal roles in acute and chronic inflammation and allergic diseases. They exert their biological effects by binding to specific G-protein-coupled receptors. Each LT receptor subtype exhibits unique functions and expression patterns. LTs play roles in various allergic diseases, including asthma (neutrophilic asthma and aspirin-sensitive asthma), allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and anaphylaxis. This review summarizes the biology of LTs and their receptors, recent developments in the area of anti-LT strategies (in settings such as ongoing clinical studies), and prospects for future therapeutic applications.

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Resolution of Inflammation in Neurodegenerative Diseases: The Role of Resolvins

Mediators of Inflammation ◽

10.1155/2020/3267172 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Sajad Chamani ◽

Vanessa Bianconi ◽

Aida Tasbandi ◽

Matteo Pirro ◽

George E. Barreto ◽

...

Keyword(s):

Neurodegenerative Diseases ◽

Neurodegenerative Disorders ◽

Acute Inflammation ◽

Current Knowledge ◽

G Protein Coupled Receptors ◽

Omega 3 ◽

Resolution Of Inflammation ◽

Proinflammatory Mediators ◽

G Protein Coupled

Acute inflammation has been described as a reactive dynamic process, promoted by the secretion of proinflammatory mediators, including lipid molecules like leukotrienes and prostaglandins, and counterbalanced by proresolving mediators including omega-3 polyunsaturated fatty-acid- (PUFA-) derived molecules. The switch from the initiation to the resolution phase of acute inflammatory response is crucial for tissue homeostasis, whereas the failure to resolve early inflammation by specialized proresolving mediators leads to chronic inflammation and tissue damage. Among PUFA-derived proresolving mediators, different eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derivatives have been described, namely, resolvins (resolution phase interaction products), which exert their anti-inflammatory and immune-regulatory activities through specific G-protein-coupled receptors. In recent years, compelling evidence has shown that impairment of resolution of inflammation is a crucial pathogenic hallmark in different neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease. This review summarizes current knowledge on the role of resolvins in resolution of inflammation and highlights available evidence showing the neuroprotective potential of EPA- and DHA-derived resolvins (E-series and D-series resolvins, respectively) in neurodegenerative diseases.

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Molecular modelling study of the role of cholesterol in the stimulation of the oxytocin receptor.

Acta Biochimica Polonica ◽

10.18388/abp.2001_5114 ◽

2001 ◽

Vol 48 (1) ◽

pp. 83-93 ◽

Cited By ~ 15

Author(s):

E Politowska ◽

R Kaźmierkiewicz ◽

V Wiegand ◽

F Fahrenholz ◽

J Ciarkowski

Keyword(s):

Molecular Modelling ◽

Oxytocin Receptor ◽

G Protein Coupled Receptors ◽

Membrane Properties ◽

In Vivo Studies ◽

Cholecystokinin Receptor ◽

Conformational Preferences ◽

G Protein Coupled

Cholesterol, an integral component of membranes in Eucaryota, is a modifier of membrane properties. In vivo studies have demonstrated that cholesterol can also modulate activities of some G protein-coupled receptors (GPCRs), which are integral membrane proteins. This can result either from an effect of cholesterol on the membrane fluidity or from specific interactions of the membrane cholesterol with the receptor, as recently demonstrated for the cholecystokinin type beta (CCKRbeta) or the oxytocin receptor (OTR). Using molecular modelling, we studied conformational preferences of cholesterol and several of its analogues. Subsequently, we simulated the distributions of their preferred conformations around the surface of OTR, CCKRbeta and a chimeric oxytocin/cholecystokinin receptor. Consequently, we suggest residues on the surface of OTR which are potentially significant in the OTR/cholesterol interaction.

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Role of G Protein-Coupled Receptors in Control of Dendritic Cell Migration

BioMed Research International ◽

10.1155/2014/738253 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Yuan Liu ◽

Guixiu Shi

Keyword(s):

G Protein ◽

Chemokine Receptors ◽

Vital Role ◽

G Protein Coupled Receptors ◽

The Body ◽

Dendritic Cell Migration ◽

Clinical Conditions ◽

Antigen Presenting ◽

G Protein Coupled

Dendritic cells (DCs) are highly efficient antigen-presenting cells. The migratory properties of DCs give them the capacity to be a sentinel of the body and the vital role in the induction and regulation of adaptive immune responses. Therefore, it is important to understand the mechanisms in control of migration of DCs to lymphoid and nonlymphoid tissues. This may provide us novel insight into the clinical treatment of diseases such as autoimmune disease, infectious disease, and tumor. The chemotactic G protein-coupled receptors (GPCR) play a vital role in control of DCs migration. Here, we reviewed the recent advances regarding the role of GPCR in control of migration of subsets of DCs, with a focus on the chemokine receptors. Understanding subsets of DCs migration could provide a rational basis for the design of novel therapies in various clinical conditions.

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Molecular Machinations: Chemokine Signals in Host-Pathogen Interactions

Clinical Microbiology Reviews ◽

10.1128/cmr.14.4.821-835.2001 ◽

2001 ◽

Vol 14 (4) ◽

pp. 821-835 ◽

Cited By ~ 55

Author(s):

Stephen W. Chensue

Keyword(s):

Chemokine Receptors ◽

Therapeutic Agents ◽

G Protein Coupled Receptors ◽

Immune Functions ◽

Microbial Infection ◽

Chemokine Production ◽

Cellular Invasion ◽

G Protein Coupled ◽

Precise Role

SUMMARY Chemokines and their G-protein-coupled receptors represent an ancient and complex system of cellular communication participating in growth, development, homeostasis and immunity. Chemokine production has been detected in virtually every microbial infection examined; however, the precise role of chemokines is still far from clear. In most cases they appear to promote host resistance by mobilizing leukocytes and activating immune functions that kill, expel, or sequester pathogens. In other cases, the chemokine system has been pirated by pathogens, especially protozoa and viruses, which have exploited host chemokine receptors as modes of cellular invasion or developed chemokine mimics and binding proteins that act as antagonists or inappropriate agonists. Understanding microbial mechanisms of chemokine evasion will potentially lead to novel antimicrobial and anti-inflammatory therapeutic agents.

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A Review on Melatonin’s Effects in Cancer: Potential Mechanisms

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520617666171121120223 ◽

2018 ◽

Vol 18 (7) ◽

pp. 985-992 ◽

Cited By ~ 3

Author(s):

Aysegul Hanikoglu ◽

Ertan Kucuksayan ◽

Rana Cagla Akduman ◽

Tomris Ozben

Keyword(s):

Systematic Review ◽

Antioxidant Activity ◽

Membrane Receptors ◽

Cancer Development ◽

Secretory Product ◽

Prevention And Treatment ◽

G Protein Coupled

This systematic review aims to elucidate the role of melatonin (N-acetyl-5-metoxy-tryptamine) (MLT) in the prevention and treatment of cancer. MLT is a pineal gland secretory product, an evolutionarily highly conserved molecule; it is also an antioxidant and an impressive protector of mitochondrial bioenergetic activity. MLT is characterized by an ample range of activities, modulating the physiology and molecular biology of the cell. Its physiological functions relate principally to the interaction of G Protein-Coupled MT1 and MT2 trans-membrane receptors (GPCRs), a family of guanidine triphosphate binding proteins. MLT has been demonstrated to suppress the growth of various tumours both, in vivo and in vitro. In this review, we analyze in depth, the antioxidant activity of melatonin, aiming to illustrate the cancer treatment potential of the molecule, by limiting or reversing the changes occurring during cancer development and growth.

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