scholarly journals Biologia Futura: stories about the functions of β2-integrins in human phagocytes

2021 ◽  
Vol 72 (1) ◽  
pp. 7-13
Author(s):  
Zsuzsa Bajtay
Keyword(s):  
Extracellular Matrix ◽  
Current Knowledge ◽  
Division Of Labour ◽  
Cellular Adhesion ◽  
Surface Proteins ◽  
Complement Receptor ◽  
Inflammatory Conditions ◽  
Complement Receptor 3 ◽  
And Migration ◽  
The Individual

AbstractIntegrins are essential membrane proteins that provide a tightly regulated link between the extracellular matrix and the intracellular cytoskeletal network. These cell surface proteins are composed of a non-covalently bound α chain and β chain. The leukocyte-specific complement receptor 3 (CR3, αMβ2, CD11b/CD18) and complement receptor 4 (CR4, αXβ2, CD11c/CD18) belong to the family of β2-integrins. These receptors bind multiple ligands like iC3b, ICAMs, fibrinogen or LPS, thus allowing them to partake in phagocytosis, cellular adhesion, extracellular matrix rearrangement and migration. CR3 and CR4 were generally expected to mediate identical functions due to their structural homology, overlapping ligand specificity and parallel expression on human phagocytes. Despite their similarities, the expression level and function of these receptors differ in a cell-type-specific manner, both under physiological and inflammatory conditions.We investigated comprehensively the individual role of CR3 and CR4 in various functions of human phagocytes, and we proved that there is a “division of labour” between these two receptors. In this review, I will summarize our current knowledge about this area.

ADAMs as mediators of EGF receptor transactivation by G protein-coupled receptors

2006 ◽  
Vol 291 (1) ◽  
pp. C1-C10 ◽  
Author(s):  
Haruhiko Ohtsu ◽  
Peter J. Dempsey ◽  
Satoru Eguchi
Keyword(s):  
G Protein ◽  
Egf Receptor ◽  
Current Knowledge ◽  
G Protein Coupled Receptors ◽  
Surface Proteins ◽  
Egf Receptors ◽  
Cellular Functions ◽  
Egfr Transactivation ◽  
And Migration ◽  
G Protein Coupled

A disintegrin and metalloprotease (ADAM) is a membrane-anchored metalloprotease implicated in the ectodomain shedding of cell surface proteins, including the ligands for epidermal growth factor (EGF) receptors (EGFR)/ErbB. It has been well documented that the transactivation of the EGFR plays critical roles for many cellular functions, such as proliferation and migration mediated through multiple G protein-coupled receptors (GPCRs). Recent accumulating evidence has suggested that ADAMs are the key metalloproteases activated by several GPCR agonists to produce a mature EGFR ligand leading to the EGFR transactivation. In this review, we describe the current knowledge on ADAMs implicated in mediating EGFR transactivation. The major focus of the review will be on the possible upstream mechanisms of ADAM activation by GPCRs as well as downstream signal transduction and the pathophysiological significances of ADAM-dependent EGFR transactivation.

scholarly journals Complement Receptor 3 Binds the Borrelia burgdorferi Outer Surface Proteins OspA and OspB in an iC3b-Independent Manner

2005 ◽  
Vol 73 (9) ◽  
pp. 6138-6142 ◽  
Author(s):  
Rodolfo C. Garcia ◽  
Rossella Murgia ◽  
Marina Cinco
Keyword(s):  
Borrelia Burgdorferi ◽  
Outer Surface ◽  
Surface Proteins ◽  
Vertebrate Host ◽  
Target Cells ◽  
Complement Receptor ◽  
Independent Manner ◽  
Outer Surface Proteins ◽  
Direct Binding ◽  
Complement Receptor 3

ABSTRACT Persistence of borreliae within the vertebrate host depends on the fate of interactions between the spirochetes and target cells. The present work demonstrates the direct binding of the Borrelia burgdorferi outer surface proteins OspA and OspB to CR3 and that this binding is independent of iC3b.

scholarly journals Modulation of Microenvironment Signals by Proteolytic Shedding of Cell Surface Extracellular Matrix Receptors

2021 ◽  
Vol 9 ◽  
Author(s):  
Yoshifumi Itoh
Keyword(s):  
Extracellular Matrix ◽  
Growth Factors ◽  
Current Knowledge ◽  
Effective Means ◽  
Receptor Ligands ◽  
Receptor Shedding ◽  
And Migration ◽  
Extracellular Matrix Receptors ◽  
Multicellular Organisms ◽  
Proteolytic Shedding

Multicellular organisms are composed of cells and extracellular matrix (ECM). ECM is a network of multidomain macromolecules that fills gaps between cells. It acts as a glue to connect cells, provides scaffolding for migrating cells, and pools cytokines and growth factors. ECM also directly sends signals to the cells through ECM receptors, providing survival signals and migration cues. Altogether, ECM provides a correct microenvironment for the cells to function in the tissue. Although ECM acts as a signaling molecule, they are insoluble solid molecules, unlike soluble receptor ligands such as cytokines and growth factors. Upon cell binding to the ECM through ECM receptors and signals transmitted, cells then need to have a mechanism to release from ECM to prevent prolonged signals, which may be tumorigenic, and migrate on ECM. One effective means to release the cells from ECM is to cleave the ECM receptors by proteinases. In this mini-review, current knowledge of ECM receptor shedding will be discussed.

scholarly journals Leptospiral Immunoglobulin-Like Domain Proteins: Roles in Virulence and Immunity

2021 ◽  
Vol 11 ◽  
Author(s):  
David A. Haake ◽  
James Matsunaga
Keyword(s):  
Extracellular Matrix ◽  
Current Knowledge ◽  
Systemic Infection ◽  
Innate Immune ◽  
Surface Proteins ◽  
Host Proteins ◽  
Complement Proteins ◽  
Specific Host ◽  
Lethal Infection ◽  
Vaccine Antigens

The virulence mechanisms required for infection and evasion of immunity by pathogenic Leptospira species remain poorly understood. A number of L. interrogans surface proteins have been discovered, lying at the interface between the pathogen and host. Among these proteins, the functional properties of the Lig (leptospiral immunoglobulin-like domain) proteins have been examined most thoroughly. LigA, LigB, and LigC contain a series of, 13, 12, and 12 closely related domains, respectively, each containing a bacterial immunoglobulin (Big) -like fold. The multidomain region forms a mostly elongated structure that exposes a large surface area. Leptospires wield the Lig proteins to promote interactions with a range of specific host proteins, including those that aid evasion of innate immune mechanisms. These diverse binding events mediate adhesion of L. interrogans to the extracellular matrix, inhibit hemostasis, and inactivate key complement proteins. These interactions may help L. interrogans overcome the physical, hematological, and immunological barriers that would otherwise prevent the spirochete from establishing a systemic infection. Despite significant differences in the affinities of the LigA and LigB proteins for host targets, their functions overlap during lethal infection of hamsters; virulence is lost only when both ligA and ligB transcription is knocked down simultaneously. Lig proteins have been shown to be promising vaccine antigens through evaluation of a variety of different adjuvant strategies. This review serves to summarize current knowledge of Lig protein roles in virulence and immunity and to identify directions needed to better understand the precise functions of the Lig proteins during infection.

scholarly journals The critical roles of histone deacetylase 3 in the pathogenesis of solid organ injury

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Li Ning ◽  
Xiong Rui ◽  
Wang Bo ◽  
Geng Qing
Keyword(s):  
Histone Deacetylase ◽  
Chromatin Remodeling ◽  
Current Knowledge ◽  
Organ Injury ◽  
Solid Organ ◽  
Solid Organ Injury ◽  
Histone Deacetylase 3 ◽  
Physiological Conditions ◽  
Inflammatory Conditions ◽  
Therapeutic Value

AbstractHistone deacetylase 3 (HDAC3) plays a crucial role in chromatin remodeling, which, in turn, regulates gene transcription. Hence, HDAC3 has been implicated in various diseases, including ischemic injury, fibrosis, neurodegeneration, infections, and inflammatory conditions. In addition, HDAC3 plays vital roles under physiological conditions by regulating circadian rhythms, metabolism, and development. In this review, we summarize the current knowledge of the physiological functions of HDAC3 and its role in organ injury. We also discuss the therapeutic value of HDAC3 in various diseases.

scholarly journals Mast Cell-Derived SAMD14 is a Novel Regulator of the Human Prostate Tumor Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1237
Author(s):  
Linda K. H. Teng ◽  
Brooke A. Pereira ◽  
Shivakumar Keerthikumar ◽  
Cheng Huang ◽  
Birunthi Niranjan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Extracellular Matrix ◽  
Tumor Microenvironment ◽  
Suppressor Gene ◽  
Prostate Tumor ◽  
Human Prostate ◽  
Proteomic Profiling ◽  
Putative Tumor Suppressor Gene ◽  
Invasion And Migration ◽  
And Migration

Mast cells (MCs) are important cellular components of the tumor microenvironment and are significantly associated with poor patient outcomes in prostate cancer and other solid cancers. The promotion of tumor progression partly involves heterotypic interactions between MCs and cancer-associated fibroblasts (CAFs), which combine to potentiate a pro-tumor extracellular matrix and promote epithelial cell invasion and migration. Thus far, the interactions between MCs and CAFs remain poorly understood. To identify molecular changes that may alter resident MC function in the prostate tumor microenvironment, we profiled the transcriptome of human prostate MCs isolated from patient-matched non-tumor and tumor-associated regions of fresh radical prostatectomy tissue. Transcriptomic profiling revealed a distinct gene expression profile of MCs isolated from prostate tumor regions, including the downregulation of SAMD14, a putative tumor suppressor gene. Proteomic profiling revealed that overexpression of SAMD14 in HMC-1 altered the secretion of proteins associated with immune regulation and extracellular matrix processes. To assess MC biological function within a model of the prostate tumor microenvironment, HMC-1-SAMD14+ conditioned media was added to co-cultures of primary prostatic CAFs and prostate epithelium. HMC-1-SAMD14+ secretions were shown to reduce the deposition and alignment of matrix produced by CAFs and suppress pro-tumorigenic prostate epithelial morphology. Overall, our data present the first profile of human MCs derived from prostate cancer patient specimens and identifies MC-derived SAMD14 as an important mediator of MC phenotype and function within the prostate tumor microenvironment.

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.

scholarly journals Immune response of calves inoculated with proteins ofAnaplasma marginale bound to an immunostimulant complex

2013 ◽  
Vol 22 (2) ◽  
pp. 253-259 ◽  
Author(s):  
Marcela Ribeiro Gasparini ◽  
Rafael Felipe da Costa Vieira ◽  
Denise Amaral Gomes do Nascimento ◽  
João Luis Garcia ◽  
Odilon Vidotto ◽  
...  
Keyword(s):  
Immune Response ◽  
Current Knowledge ◽  
Surface Proteins ◽  
Control Group ◽  
Humoral Immune ◽  
The Third ◽  
Additional Testing ◽  
Major Surface Proteins ◽  
Cattle Herds ◽  
Major Surface

Despite our current knowledge of the immunology, pathology, and genetics of Anaplasma marginale, prevention in cattle is currently based on old standbys, including live attenuated vaccines, antibiotic treatment, and maintaining enzootic stability in cattle herds. In the present study, we evaluated the use of an immunostimulant complex (ISCOMATRIX) adjuvant, associated with a pool of recombinant major surface proteins (rMSP1a, rMSP1b, rMSP4 and rMSP5) to improve the humoral immune response triggered in calves mainly by IgG2. Ten calves were divided in three groups: 4 calves were inoculated with the ISCOMATRIX/rMSPs (G1); 2 calves were inoculated with ISCOMATRIX adjuvant (G2); and 4 calves received saline (G3). Three inoculations were administered at 21-day intervals. In G1, the calves showed significant increases in total IgG, IgG1 and IgG2 levels 21 days after the second inoculation, compared to the control group (p < 0.05), and G1 calves remained above the cut-off value 28 days after the third inoculation (p < 0.05). The post-immunized sera from calves in G1 reacted specifically for each of the rMSPs used. In conclusion, the ISCOMATRIX/rMSPs induced antigen-specific seroconversion in calves. Therefore, additional testing to explore the protection induced by rMSPs, both alone and in conjunction with proteins previously identified as subdominant epitopes, is warranted.

scholarly journals β-Glucan enhances complement-mediated hematopoietic recovery after bone marrow injury

Blood ◽  
2006 ◽  
Vol 107 (2) ◽  
pp. 835-840 ◽  
Author(s):  
Daniel E. Cramer ◽  
Daniel J. Allendorf ◽  
Jarek T. Baran ◽  
Richard Hansen ◽  
Jose Marroquin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mouse Serum ◽  
Complement Receptor ◽  
Dependent Manner ◽  
Complement Receptor 3 ◽  
Total Body ◽  
Stimulating Factor ◽  
Sublethal Irradiation ◽  
Classic Pathway

AbstractMyelotoxic injury in the bone marrow (BM) as a consequence of total body irradiation (TBI) or granulocyte colony-stimulating factor (G-CSF) mobilization results in the deposition of iC3b on BM stroma (stroma-iC3b). In the present study, we have examined how stroma-iC3b interacts with hematopoietic progenitor cells (HPCs) and the role of complement (C) and complement receptor 3 (CR3) in BM injury/repair. We demonstrate here that stroma-iC3b tethers HPCs via the inserted (I) domain of HPC complement receptor 3 (CR3, CD11b/CD18, Mac-1). Following irradiation, stroma-iC3b was observed in the presence of purified IgM and normal mouse serum (NMS), but not serum from Rag-2-/- mice, implicating a role for antibody (Ab) and the classic pathway of C activation. Furthermore, a novel role for soluble yeast β-glucan, a ligand for the CR3 lectin-like domain (LLD), in the priming of CR3+ HPC is suggested. Soluble yeast β-glucan could enhance the proliferation of tethered HPCs, promote leukocyte recovery following sublethal irradiation, and increase the survival of lethally irradiated animals following allogeneic HPC transplantation in a CR3-dependent manner. Taken together, these observations suggest a novel role for C, CR3, and β-glucan in the restoration of hematopoiesis following injury. (Blood. 2006;107:835-840)

Mental health in a conflict area: Migration, economic stress and religiosity in the three southernmost provinces of Thailand

2016 ◽  
Vol 63 (2) ◽  
pp. 91-98 ◽  
Author(s):  
Kathleen Ford ◽  
Aree Jampaklay ◽  
Aphichat Chamratrithirong
Keyword(s):  
Mental Health ◽  
Multilevel Models ◽  
Psychiatric Symptoms ◽  
Economic Stress ◽  
Economic Effects ◽  
World Health ◽  
Thai Government ◽  
And Migration ◽  
The Individual ◽  
Self Reporting Questionnaire

Aim: Three southern provinces of Thailand, Pattani, Yala and Narathiwat, have been involved in a long period of unrest due to differences between the population in the provinces and the Thai government with regard to language, culture and governance. The objectives of this article are to examine the effects of everyday stressors due to the conflict, including economic stress and migration, as well as the effect of religiosity on the reporting of psychiatric symptoms among adults in the three provinces. Methods: Data were drawn from a survey conducted in 2014. The survey included a probability sample of 2,053 Muslim adults aged 18–59 years.Mental health was assessed using World Health Organization’s (WHO) Self-Reporting Questionnaire (SRQ) of 20 questions. Multilevel models were estimated to examine the influence of economic stress due to the conflict, as well as community and individual aspects of migration and religion on mental health. Results: The data showed that migration from the household and the community and the economic effects of the unrest were associated with reporting of more psychiatric symptoms among adults in the southern provinces. Religion was related to reporting of fewer psychiatric symptoms at the individual and the community levels. Conclusion: The study documented increased reporting of psychiatric symptoms among persons reporting perceived household economic stress due to the conflict and the migration of family members.

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