scholarly journals Resident and elicited macrophages differ in expression of their glycomes and lectins

2020 ◽  
Author(s):  
Diane D. Park ◽  
Jiaxuan Chen ◽  
Matthew R. Kudelka ◽  
Nan Jia ◽  
Carolyn A. Haller ◽  
...  
Keyword(s):  
Protein Complexes ◽  
Peritoneal Macrophages ◽  
Immune Defense ◽  
Complex Type ◽  
Acetylneuraminic Acid ◽  
Acid Ratio ◽  
Lectin Genes ◽  
Extended Complex ◽  
Pleiotropic Functions ◽  
Cellular Polarization

AbstractThe pleiotropic functions of macrophages in immune defense, tissue repair, and maintenance of tissue homeostasis are supported by the heterogeneity in macrophage sub-populations that differ both in ontogeny and polarization. Although glycans and lectins are integral to macrophage function, little is known about the factors governing their expression. Here we show that the cellular glycome of murine peritoneal macrophages primarily reflects developmental origin and to a lesser degree, cellular polarization. Resident macrophages were characterized by a simple glycome, predominantly consisting of core 1 O-glycans, while elicited macrophages also expressed core 2 O-glycans, along with highly branched and extended complex-type N-glycans, that exhibited a higher N-acetylneuraminic acid:N-glycolylneuraminic acid ratio. Strikingly, our analysis revealed that resident and elicited macrophages express 139 lectin genes, with differential expression of 49 lectin genes, including galectins, Siglecs, and C-type lectins. These results suggest that regulation of self-glycan-protein complexes may be central to macrophage residence and recruitment.

Interaction with complement proteins and dendritic cells implicates LCCL domain-containing proteins (CCps) of malaria parasites in immunomodulation

2018 ◽  
Vol 475 (21) ◽  
pp. 3311-3314 ◽  
Author(s):  
Puran Singh Sijwali
Keyword(s):  
Dendritic Cells ◽  
Complement System ◽  
Protein Complexes ◽  
Immune Defense ◽  
Malaria Parasites ◽  
Classical Complement Pathway ◽  
Soluble Immune Complexes ◽  
Multimeric Protein ◽  
The Complement System

The evasion of host immune defense is critical for pathogens to invade, establish infection and perpetuate in the host. The complement system is one of the first lines of innate immune defense in humans that destroys pathogens in the blood circulation. Activation of the complement system through direct encounter with pathogens or some other agents leads to osmolysis of pathogens, clearance of soluble immune complexes and recruitment of lymphocytes at the site of activation. Although malaria parasites are not exposed to the complement system owing to their intracellular development for most part of their life cycle in the human host, the extracellular stages must face the complement system of human or mosquito or both. In a recent issue of the Biochemical Journal, Sharma et al. reported that Plasmodiumfalciparum LCCL domain-containing protein 1 (PfCCp1) inhibited activation of the classical complement pathway and down-regulated effector responses of dendritic cells, which implicate PfCCp1 and related proteins in immunomodulation of the host that likely benefits the parasite. PfCCp1 belongs to a multi-domain protein family that exists as multimeric protein complexes. It needs to be investigated whether PfCCp1 or its multimeric protein complexes have an immunomodulatory effect in vivo and on the mosquito complement system

scholarly journals Updating the NLRC4 Inflammasome: from Bacterial Infections to Autoimmunity and Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiexia Wen ◽  
Bin Xuan ◽  
Yang Liu ◽  
Liwei Wang ◽  
Li He ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Molecular Mechanisms ◽  
Protein Complexes ◽  
Immune Defense ◽  
Innate Immune ◽  
Sensor Protein ◽  
Different Types ◽  
Microbial Infections ◽  
Activation Mechanisms ◽  
Specific Protease

Inflammasomes comprise a family of cytosolic multi-protein complexes that modulate the activation of cysteine-aspartate-specific protease 1 (caspase-1) and promote the maturation and secretion of interleukin (IL)-1β and IL-18, leading to an inflammatory response. Different types of inflammasomes are defined by their sensor protein which recognizes pathogenic ligands and then directs inflammasome assembly. Although the specific molecular mechanisms underlying the activation of most inflammasomes are still unclear, NLRC4 inflammasomes have emerged as multifaceted agents of the innate immune response, playing important roles in immune defense against a variety of pathogens. Other studies have also expanded the scope of NLRC4 inflammasomes to include a range of inherited human autoimmune diseases as well as proposed roles in cancer. In this review article, we provide an updated overview of NLRC4 inflammasomes, describing their composition, activation mechanisms and roles in both microbial infections and other disease conditions.

LIPID–PROTEIN COMPLEXES IN MEMBRANES OF NERVOUS TISSUE

1962 ◽  
Vol 40 (1) ◽  
pp. 1261-1271
Author(s):  
L. S. Wolfe
Keyword(s):  
Nervous System ◽  
Sialic Acid ◽  
Schwann Cell ◽  
Myelin Sheath ◽  
Nervous Tissue ◽  
Chemical Structure ◽  
Grey Matter ◽  
Protein Complexes ◽  
Functional Importance ◽  
Acetylneuraminic Acid

Recent investigations have demonstrated that cellular and intracellular membranes within the nervous system contain complex associations of lipids, proteins, and carbohydrates. The myelin sheath contains such complexes derived from the Schwann cell or satellite cell membranes. Similar complexes are found in membranes from grey matter together with less familiar associations between lipids and carbohydrates. Gangliosides are a group of acidic glycolipids which contain among other sugars the sialic acid, N-acetylneuraminic acid. The present state of knowledge on the chemical structure, metabolism, and functional importance of these complex macromolecules is discussed.

scholarly journals Roles for thrombin and fibrin(ogen) in cytokine/chemokine production and macrophage adhesion in vivo

Blood ◽  
2002 ◽  
Vol 99 (3) ◽  
pp. 1053-1059 ◽  
Author(s):  
Frank M. Szaba ◽  
Stephen T. Smiley
Keyword(s):  
Inflammatory Responses ◽  
Direct Injection ◽  
Peritoneal Macrophages ◽  
Dependent Manner ◽  
Chemokine Production ◽  
Monocyte Chemoattractant Protein 1 ◽  
Macrophage Adhesion ◽  
Pleiotropic Functions ◽  
Deficient Mice

Abstract Extravascular coagulation leading to fibrin deposition accompanies many immune and inflammatory responses. Although recognized by pathologists for decades, and probably pathologic under certain conditions, the physiologic functions of extravascular coagulation remain to be fully defined. This study demonstrates that thrombin can activate macrophage adhesion and prompt interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) production in vivo. Peritoneal macrophages were elicited with thioglycollate (TG) and then activated in situ, either by intraperitoneal injection of lipopolysaccharide (LPS) or by injection of antigen into mice bearing antigen-primed T cells. Others previously established that such treatments stimulate macrophage adhesion to the mesothelial lining of the peritoneal cavity. The present study demonstrates that thrombin functions in this process, as macrophage adhesion was suppressed by Refludan, a highly specific thrombin antagonist, and induced by direct peritoneal administration of purified thrombin. Although recent studies established that protease activated receptor 1 (PAR-1) mediates some of thrombin's proinflammatory activities macrophage adhesion occurred normally in PAR-1–deficient mice. However, adhesion was suppressed in fibrin(ogen)-deficient mice, suggesting that fibrin formation stimulates macrophage adhesion in vivo. This study also suggests that fibrin regulates chemokine/cytokine production in vivo, as direct injection of thrombin stimulated peritoneal accumulation of IL-6 and MCP-1 in a fibrin(ogen)-dependent manner. Given that prior studies have clearly established inflammatory roles for PAR-1, thrombin probably has pleiotropic functions during inflammation, stimulating vasodilation and mast cell degranulation via PAR-1, and activating cytokine/chemokine production and macrophage adhesion via fibrin(ogen).

scholarly journals USP21 negatively regulates antiviral response by acting as a RIG-I deubiquitinase

2014 ◽  
Vol 211 (2) ◽  
pp. 313-328 ◽  
Author(s):  
Yihui Fan ◽  
Renfang Mao ◽  
Yang Yu ◽  
Shangfeng Liu ◽  
Zhongcheng Shi ◽  
...  
Keyword(s):  
Rna Virus ◽  
Peritoneal Macrophages ◽  
Antiviral Response ◽  
Negative Regulation ◽  
Immune Defense ◽  
Negative Regulator ◽  
Chimeric Mice ◽  
Antiviral Responses ◽  
Bona Fide ◽  
Deficient Mice

Lys63-linked polyubiquitination of RIG-I is essential in antiviral immune defense, yet the molecular mechanism that negatively regulates this critical step is poorly understood. Here, we report that USP21 acts as a novel negative regulator in antiviral responses through its ability to bind to and deubiquitinate RIG-I. Overexpression of USP21 inhibited RNA virus–induced RIG-I polyubiquitination and RIG-I–mediated interferon (IFN) signaling, whereas deletion of USP21 resulted in elevated RIG-I polyubiquitination, IRF3 phosphorylation, IFN-α/β production, and antiviral responses in MEFs in response to RNA virus infection. USP21 also restricted antiviral responses in peritoneal macrophages (PMs) and bone marrow–derived dendritic cells (BMDCs). USP21-deficient mice spontaneously developed splenomegaly and were more resistant to VSV infection with elevated production of IFNs. Chimeric mice with USP21-deficient hematopoietic cells developed virus-induced splenomegaly and were more resistant to VSV infection. Functional comparison of three deubiquitinases (USP21, A20, and CYLD) demonstrated that USP21 acts as a bona fide RIG-I deubiquitinase to down-regulate antiviral response independent of the A20 ubiquitin-editing complex. Our studies identify a previously unrecognized role for USP21 in the negative regulation of antiviral response through deubiquitinating RIG-I.

scholarly journals The Role of Sialic Acid in Opsonin-Dependent and Opsonin-Independent Adhesion of Listeria monocytogenesto Murine Peritoneal Macrophages

1998 ◽  
Vol 66 (2) ◽  
pp. 620-626 ◽  
Author(s):  
Srinivas Maganti ◽  
Marcia M. Pierce ◽  
Alex Hoffmaster ◽  
Frank G. Rodgers
Keyword(s):  
Sialic Acid ◽  
Acid Group ◽  
Peritoneal Macrophages ◽  
Host Cells ◽  
Mouse Serum ◽  
Sodium Metaperiodate ◽  
Acetylneuraminic Acid ◽  
Humoral Immune ◽  
Murine Peritoneal Macrophages ◽  
Complement Receptor 3

ABSTRACT The adhesion of listeriae to host cells employs mechanisms which are complex and not well understood. Listeria monocytogenesis a facultative intracellular pathogen responsible for meningoencephalitis, septicemia, and abortion in susceptible and immunocompromised individuals. Subsequent to colonization and penetration of the gut epithelium, the organism attaches to resident macrophages and replicates intracellularly, thus evading the humoral immune system of the infected host. The focus of these studies was to investigate the attachment of the organism to murine peritoneal macrophages in an opsonin-dependent and opsonin-independent fashion. Assessment of competitive binding experiments by immunofluorescence and enzyme-linked immunosorbent assays showed that adhesion of the organism to macrophages in the presence or absence of opsonins was inhibited (90%) by N-acetylneuraminic acid (NAcNeu). In addition, the lectin from Maackia amurensis, with affinity for NAcNeu-α(2,3)galactose, blocked binding of L. monocytogenes to host cells. Oxidation of the surface carbohydrates on the organism by using sodium metaperiodate resulted in a dose-dependent reduction (up to 98%) in adherence to macrophages. Monoclonal antibody to complement receptor 3 did not prevent listeriae from binding to mouse macrophages or from replicating within the infected cells whether or not normal mouse serum was present. Based on our results, we propose the involvement of NAcNeu, a member of the sialic acid group, in the attachment of L. monocytogenes to permissive murine macrophages.

LIPID–PROTEIN COMPLEXES IN MEMBRANES OF NERVOUS TISSUE

1962 ◽  
Vol 40 (9) ◽  
pp. 1261-1271 ◽  
Author(s):  
L. S. Wolfe
Keyword(s):  
Nervous System ◽  
Sialic Acid ◽  
Schwann Cell ◽  
Myelin Sheath ◽  
Nervous Tissue ◽  
Chemical Structure ◽  
Grey Matter ◽  
Protein Complexes ◽  
Functional Importance ◽  
Acetylneuraminic Acid

Recent investigations have demonstrated that cellular and intracellular membranes within the nervous system contain complex associations of lipids, proteins, and carbohydrates. The myelin sheath contains such complexes derived from the Schwann cell or satellite cell membranes. Similar complexes are found in membranes from grey matter together with less familiar associations between lipids and carbohydrates. Gangliosides are a group of acidic glycolipids which contain among other sugars the sialic acid, N-acetylneuraminic acid. The present state of knowledge on the chemical structure, metabolism, and functional importance of these complex macromolecules is discussed.

scholarly journals Viral Interactions with Adaptor-Protein Complexes: A Ubiquitous Trait among Viral Species

2021 ◽  
Vol 22 (10) ◽  
pp. 5274
Author(s):  
Ivana Strazic Geljic ◽  
Paola Kucan Brlic ◽  
Lucija Musak ◽  
Dubravka Karner ◽  
Andreja Ambriović-Ristov ◽  
...  
Keyword(s):  
Protein Trafficking ◽  
Protein Complexes ◽  
Adaptor Protein ◽  
Cellular Protein ◽  
Immune Defense ◽  
Membrane Structures ◽  
Transport Pathways ◽  
Viral Propagation ◽  
Causative Agents ◽  
Mediate Cell

Numerous viruses hijack cellular protein trafficking pathways to mediate cell entry or to rearrange membrane structures thereby promoting viral replication and antagonizing the immune response. Adaptor protein complexes (AP), which mediate protein sorting in endocytic and secretory transport pathways, are one of the conserved viral targets with many viruses possessing AP-interacting motifs. We present here different mechanisms of viral interference with AP complexes and the functional consequences that allow for efficient viral propagation and evasion of host immune defense. The ubiquity of this phenomenon is evidenced by the fact that there are representatives for AP interference in all major viral families, covered in this review. The best described examples are interactions of human immunodeficiency virus and human herpesviruses with AP complexes. Several other viruses, like Ebola, Nipah, and SARS-CoV-2, are pointed out as high priority disease-causative agents supporting the need for deeper understanding of virus-AP interplay which can be exploited in the design of novel antiviral therapies.

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