scholarly journals Inside-out Signalling From Aminopeptidase N (CD13) To Complement Receptor 3 (CR3, CD11b/CD18)

2021 ◽  
Author(s):  
Laura Díaz-Alvarez ◽  
Mariana Esther Martinez-Sánchez ◽  
Eleanor Gray ◽  
Enrique Ortega
Keyword(s):  
Receptor Tyrosine Kinase ◽  
Human Monocyte ◽  
Aminopeptidase N ◽  
Integrated Analysis ◽  
Complement Receptor ◽  
Monocytes And Macrophages ◽  
Complement Receptor 3 ◽  
Inside Out ◽  
Signalling Cascade ◽  
Selection Of

Upon ligand engagement, certain receptors can activate an integrin through a mechanism called inside-out signalling. This phenomenon prepares the cell for the next steps of the process it will perform. CR3 (Complement receptor 3), the most abundant β2 integrin in monocytes and macrophages, and CD13 (aminopeptidase N) are two immune receptors with overlapping activities: adhesion, phagocytosis of opsonized particles, and respiratory burst induction. They can be found together in functional signalling microdomains, or lipid rafts, on the surface of human leukocytes. Thus, given their common functions, shared physical location and the fact that some phagocytic and adhesion receptors activate a selection of integrins, we hypothesized that CD13 could activate CR3 through an inside-out signalling mechanism. To test this hypothesis, we first ascertained the activation of CR3 after CD13 crosslinking in human monocyte-derived macrophages. We used an integrated analysis of bioinformatics and experimental data to suggest two possible signalling cascades that could explain the phenomenon. Finally, we show that the non-receptor tyrosine kinase Syk is a key attenuator of this pathway. Our results demonstrated that, even in the absence of canonical signalling motifs, and despite having a noticeably short cytoplasmic tail (7-10 amino acids), CD13 was capable of triggering an inside-out signalling cascade, adding a new function to those already known for this moonlighting protein.

scholarly journals CD44-mediated phagocytosis induces inside-out activation of complement receptor-3 in murine macrophages

Blood ◽  
2007 ◽  
Vol 110 (13) ◽  
pp. 4492-4502 ◽  
Author(s):  
Eric Vachon ◽  
Raiza Martin ◽  
Vivian Kwok ◽  
Vera Cherepanov ◽  
Chung-Wai Chow ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Immunofluorescence Microscopy ◽  
Complement Receptor ◽  
Fcγ Receptors ◽  
Intracellular Signaling Pathways ◽  
Large Particles ◽  
Complement Receptor 3 ◽  
Inside Out ◽  
Β2 Integrins

Diverse receptors, including Fcγ receptors and β2 integrins (complement receptor-3 [CR3], CD11b/CD18), have been implicated in phagocytosis, but their distinct roles and interactions with other receptors in particle engulfment are not well defined. CD44, a transmembrane adhesion molecule involved in binding and metabolism of hyaluronan, may have additional functions in regulation of inflammation and phagocytosis. We have recently reported that CD44 is a fully competent phagocytic receptor that is able to trigger ingestion of large particles by macrophages. Here, we investigated the role of coreceptors and intracellular signaling pathways in modulation of CD44-mediated phagocytosis. Using biotinylated erythrocytes coated with specific antibodies (anti-CD44–coated erythrocytes [Ebabs]) as the phagocytic prey, we determined that CD44-mediated phagocytosis is reduced by 45% by a blocking CD11b antibody. Further, CD44-mediated phagocytosis was substantially (42%) reduced in CD18-null mice. Immunofluorescence microscopy revealed that CD11b is recruited to the phagocytic cup. The mechanism of integrin activation and mobilization involved activation of the GTPase Rap1. CD44-mediated phagocytosis was also sensitive to the extracellular concentration of the divalent cation Mg2+ but not Ca2+. In addition, buffering of intracellular Ca2+ did not affect CD44-mediated phagocytosis. Taken together, these data suggest that CD44 stimulation induces inside-out activation of CR3 through the GTPase Rap1.

scholarly journals Immune modulation by complement receptor 3-dependent human monocyte TGF-β1-transporting vesicles

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Luke D. Halder ◽  
Emeraldo A. H. Jo ◽  
Mohammad Z. Hasan ◽  
Marta Ferreira-Gomes ◽  
Thomas Krüger ◽  
...  
Keyword(s):  
Immune Modulation ◽  
Human Monocyte ◽  
Complement Receptor ◽  
Complement Receptor 3 ◽  
Tgf Β1

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)

scholarly journals Carnavalesk taalgebruik en de constructie van lokale identiteiten

2012 ◽  
Vol 1 (1) ◽  
pp. 15-40 ◽  
Author(s):  
Leonie M.E.A. Cornips ◽  
Vincent de Rooij ◽  
Irene Stengs
Keyword(s):  
Interdisciplinary Approach ◽  
Integrated Analysis ◽  
Cultural Elements ◽  
Language And Culture ◽  
Norms And Values ◽  
Southern Netherlands ◽  
Interdisciplinary Study ◽  
The City ◽  
Selection Of

This article aims to encourage the interdisciplinary study of ‘languaculture,’ an approach to language and culture in which ideology, linguistic and cultural forms, as well as praxis are studied in relation to one another. An integrated analysis of the selection of linguistic and cultural elements provides insight into how these choices arise from internalized norms and values, and how people position themselves toward received categories and hegemonic ideologies. An interdisciplinary approach will stimulate a rethinking of established concepts and methods of research. It will also lead to a mutual strengthening of linguistic, sociolinguistic, and anthropological research. This contribution focuses on Limburg and the linguistic political context of this Southern-Netherlands region where people are strongly aware of their linguistic distinctiveness. The argument of the paper is based on a case study of languaculture, viz. the carnivalesque song ‘Naar Talia’ (To Italy) by the Getske Boys from the city of Heerlen.

scholarly journals Thymosin α1 Activates Complement Receptor-Mediated Phagocytosis in Human Monocyte-Derived Macrophages

2013 ◽  
Vol 6 (1) ◽  
pp. 72-88 ◽  
Author(s):  
Annalucia Serafino ◽  
Francesca Pica ◽  
Federica Andreola ◽  
Roberta Gaziano ◽  
Noemi Moroni ◽  
...  
Keyword(s):  
Human Monocyte ◽  
Complement Receptor

scholarly journals Differential interleukin-1 elaboration by density-defined human monocyte subpopulations

Blood ◽  
1985 ◽  
Vol 66 (2) ◽  
pp. 298-301
Author(s):  
JA Elias ◽  
P Chien ◽  
KM Gustilo ◽  
AD Schreiber
Keyword(s):  
Human Blood ◽  
Interleukin 1 ◽  
Human Monocyte ◽  
Mononuclear Phagocytes ◽  
Blood Monocyte ◽  
Thymocyte Proliferation ◽  
Percoll Gradients ◽  
Human Blood Monocyte ◽  
Monocytes And Macrophages ◽  
Monocyte Subpopulations

Interleukin-1 (IL-1) is an important immunoregulatory peptide produced by monocytes and macrophages. Because mononuclear phagocytes are morphologically and functionally heterogeneous, we examined whether they differ in their ability to elaborate IL-1. We used discontinuous Percoll gradients to obtain five density-defined human blood monocyte subpopulations. Unfractionated monocytes and their subsets were compared for their ability to stimulate thymocyte proliferation. Supernatants obtained from the denser monocytes consistently contained more IL-1 activity than did supernatants from the less dense cells. This difference in IL-1 activity was the result of differences in IL-1 elaboration, not the selective production of an inhibitor of IL-1- induced thymocyte proliferation. These data demonstrate that density- defined human monocyte subpopulations differ in their capacity to elaborate IL-1.

scholarly journals Selection of biomarkers for HIV-1 latency by integrated analysis

Genomics ◽  
2019 ◽  
Vol 111 (3) ◽  
pp. 327-333 ◽  
Author(s):  
Sun Young Lee ◽  
Byeong-Sun Choi ◽  
Cheol-Hee Yoon ◽  
Chun Kang ◽  
Kisoon Kim ◽  
...  
Keyword(s):  
Integrated Analysis ◽  
Hiv 1 ◽  
Selection Of

scholarly journals Paracrine downregulation of Fc gamma RIII in human monocyte-derived macrophages induced by phagocytosis of nonopsonized particles

Blood ◽  
1994 ◽  
Vol 83 (8) ◽  
pp. 2294-2304 ◽  
Author(s):  
G Liao ◽  
J Simone ◽  
SR Simon
Keyword(s):  
Direct Contact ◽  
Human Monocyte ◽  
Tnf Alpha ◽  
Triggered Release ◽  
Necrosis Factor Alpha ◽  
Dual Channel ◽  
Latex Beads ◽  
Monocytes And Macrophages ◽  
Channel Analysis ◽  
Green Fluorescent

Abstract Monocytes and macrophages can take up nonopsonized particles through a direct phagocytic process and IgG-coated particles through combined mechanisms of nonspecific phagocytosis and internalization mediated by specific Fc receptors for IgG (Fc gamma R) on the plasma membrane. In this study, we report the effect of phagocytosis of nonopsonized latex beads on the levels of expression of Fc gamma receptors in human monocyte-derived macrophages (MDM) as measured by flow cytometry (fluorescence-activated cell sorter [FACS]). Macrophages were exposed to green fluorescent 1-micron polystyrene beads before labeling for Fc gamma RI, Fc gamma R-II, and Fc gamma R-III, respectively, with 32.2, 2E1, and 3G8 monoclonal antibodies (MoAbs) and a phycoerythrin (PE)- conjugated secondary Ab to permit dual-channel analysis of fluorescence intensity by FACS. Macrophages that had phagocytosed at least one bead showed reduced levels of surface Fc gamma R-III but not Fc gamma R-I or Fc gamma R-II when compared with cells that had never been exposed to beads. Moreover, cells that were not in direct contact with beads, but that shared medium with cells that had phagocytosed beads also had reduced levels of Fc gamma R-III but not Fc gamma R-I or Fc gamma R-II, suggesting a cytokine-mediated mechanism of Fc gamma R-III downregulation. Phagocytosis of 1-micron beads alone stimulated macrophages to release tumor necrosis factor-alpha (TNF-alpha). The medium from macrophages phagocytosing beads could stimulate other macrophages not in direct contact with beads to release TNF-alpha as well, but such paracrine-triggered release could be reduced by more than 50% if the medium from the phagocytosing cells was first treated with a neutralizing anti-TNF-alpha antibody. Moreover, the paracrine downregulation of Fc gamma R-III described above could also be blocked if the neutralizing anti-TNF-alpha antibody was added to the medium of phagocytosing cells. Treatment of macrophages with recombinant human TNF-alpha in the absence of beads induced decreased levels of Fc gamma R-III but not of Fc gamma R-II. These results show that paracrine downregulation of Fc gamma R-III is mediated by a TNF-alpha-dependent mechanism.

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