Differential effects of the complement peptides, C5a and C5a des Arg on human basophil and lung mast cell histamine release.

Schulman, Edward S.; Post, Thomas J.; Henson, Peter M.; Giclas, Patricia C.

doi:10.1172/jci113403

Cited by 100 publications

(56 citation statements)

References 34 publications

(14 reference statements)

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“…Chymase inhibitors block IgE-mediated histamine release from skin MCs (predominantly MC TC ) but not from ''normal'' lung MCs (predominantly MC T ) (18). Similar phenotypic differences in response to C5a and compound 48/80 are also seen (19,20). In addition, generation of prostaglandin (PG) D2 may be more pronounced in MC TC and not always associated with MC degranulation (21,22).…”

Section: What This Study Adds To the Fieldmentioning

confidence: 90%

Mast Cell Phenotype, Location, and Activation in Severe Asthma

Balzar¹,

Fajt²,

Comhair³

et al. 2011

Am J Respir Crit Care Med

270

242

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Rationale: Severe asthma (SA) remains poorly understood. Mast cells (MC) are implicated in asthma pathogenesis, but it remains unknown how their phenotype, location, and activation relate to asthma severity. Objectives: To compare MC-related markers measured in bronchoscopically obtained samples with clinically relevant parameters between normal subjects and subjects with asthma to clarify their pathobiologic importance. Methods: Endobronchial biopsies, epithelial brushings, and bronchoalveolar lavage were obtained from subjects with asthma and normal subjects from the Severe Asthma Research Program (N 5 199). Tryptase, chymase, and carboxypeptidase A (CPA)3 were used to identify total MC (MC Tot ) and the MC TC subset (MCs positive for both tryptase and chymase) using immunostaining and quantitative real-time polymerase chain reaction. Lavage was analyzed for tryptase and prostaglandin D2 (PGD2) by ELISA. Measurements and Main Results: Submucosal MC Tot (tryptase-positive by immunostaining) numbers were highest in ''mild asthma/no inhaled corticosteroid (ICS) therapy'' subjects and decreased with greater asthma severity (P 5 0.002). In contrast, MC TC (chymasepositive by immunostaining) were the predominant (MC TC /MC Tot . 50%) MC phenotype in SA (overall P 5 0.005). Epithelial MC Tot were also highest in mild asthma/no ICS, but were not lower in SA. Instead, they persisted and were predominantly MC TC . Epithelial CPA3 and tryptase mRNA supported the immunostaining data (overall P 5 0.008 and P 5 0.02, respectively). Lavage PGD2 was higher in SA than in other steroid-treated groups (overall P 5 0.02), whereas tryptase did not differentiate the groups. In statistical models, PGD2 and MC TC /MC Tot predicted SA. Conclusions: Severe asthma is associated with a predominance of MC TC in the airway submucosa and epithelium. Activation of those MC TC may contribute to the increases in PGD2 levels. The data suggest an altered and active MC population contributes to SA pathology.

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Section: What This Study Adds To the Fieldmentioning

confidence: 90%

Mast Cell Phenotype, Location, and Activation in Severe Asthma

Balzar¹,

Fajt²,

Comhair³

et al. 2011

Am J Respir Crit Care Med

270

242

View full text Add to dashboard Cite

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“…It is well known, however, that C5a is by far the most potent of all three anaphylatoxins, whereas C4a is the weakest in inducing biologically relevant responses (3). C5a plays an important role in promoting: 1) chemotaxis to a variety of leukocytes, including neutrophils and macrophages (2,4,5); 2) activation of the respiratory burst in phagocytes (6); 3) expression of TNF-␣ and IL-6 in monocyte-derived macrophages (7) as well as expression of IL-1␤, RANTES, and IL-8 in umbilical vein endothelial cells (8); 4) production of PGs and eicosanoids (9); 5) release of histamine by mast cells and basophils (10,11); and 6) up-regulation of CR3 (12,13) and P-selectin (14). In addition, C5a has been shown to play an important role in adaptive immunity.…”

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confidence: 99%

Cloning, Expression, Cellular Distribution, and Role in Chemotaxis of a C5a Receptor in Rainbow Trout: The First Identification of a C5a Receptor in a Nonmammalian Species

Boshra

Peters

et al. 2004

The Journal of Immunology

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C3a, C4a, and C5a anaphylatoxins generated during complement activation play a key role in inflammation. C5a is the most potent of the three anaphylatoxins in eliciting biological responses. The effects of C5a are mediated by its binding to C5a receptor (C5aR, CD88). To date, C5aR has only been identified and cloned in mammalian species, and its evolutionary history remains ill-defined. To gain insights into the evolution, conserved structural domains, and functions of C5aR, we have cloned and characterized a C5aR in rainbow trout, a teleost fish. The isolated cDNA encoded a 350-aa protein that showed the highest sequence similarity to C5aR from other species. Genomic analysis revealed the presence of one continuous exon encoding the entire open reading frame. Northern blot analysis showed significant expression of the trout C5a receptor (TC5aR) message in PBLs and kidney. Flow cytometric analysis showed that two Abs generated against two different areas of the extracellular N-terminal region of TC5aR positively stained the same leukocyte populations from PBLs. B lymphocytes and granulocytes comprised the majority of cells recognized by the anti-TC5aR. More importantly, these Abs inhibited chemotaxis of PBLs toward a chemoattractant fraction purified from complement-activated trout serum. Our data suggest that the split between C5aR and C3aR from a common ancestral molecule occurred before the emergence of teleost fish. Moreover, we demonstrate that the overall structure of C5aR as well as its role in chemotaxis have remained conserved for >300 million years.

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“…The significance of this study lies on the fact that the complement activation of the samples (nanomaterials and medical devices) was determined by the C5c in an attempt to link this factor with surfaces at nanoscale and improve their immunocompatibility. In other studies, the complement system is involved in chronic inflammatory processes and especially the components C3a and C5a exert strong chemotactic and proinflammatory effects [15][16][17][18][19]. Spiedl et.al.…”

Section: Contact Angle Measurementsmentioning

confidence: 99%

IN-VITRO IMMUNOCOMPATIBILITY & CHARACTERIZATION AT NANOSCALE OF THIN FILMS AND VASCULAR MEDICAL DEVICES.

Janjic¹,

Kavatzikidou²,

Karagkiozaki³

et al. 2017

IJAR

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Texture.Immunocompatibility comprises a complex response which depends both on the physico-chemical characteristics of the biomaterial and on the hereditary and acquired ability of the recipient to react. Objective: The objective of the present work was the comparative study of the immunocompatibility of different materials and their morphological characterization. Methods: The three types of thin films used in this work were the titanium nitride [TiN],Titanium [Ti] and the amorphous hydrogenated diamond-like carbon [a-C:H], which are deposited onto a silicon substrate by Magnetron Sputtering and Plasma-Enhanced Chemical Vapor Deposition (PECVD), respectively. Medical devices used in this study, were the silicon coated Latex irrigation catheter and the endoprosthesis such as vascular grafts [Dacron, PTFE] and stent grafts [Nitinol stent graft, Cobalt Chromium stent graft]. Bare silicon substrate and serum were used as a "negative" control and the Latex [elastomer-elastic hydrocarbon polymer] as a "positive" control. Complement C5 convertase [C5c] activation was assessed using the sandwich enzyme immunoassay-sandwich ELISA for the specific time periods [0min, 15 min, 30 min and 60 min] at wavelength of 450nm. The morphological characterization of the materials was conducted by Scanning Electron Microscopy (SEM). The study of biomaterials topography was conducted by Atomic Force Microscopy (AFM) and their surface wettability properties by Contact Angle measurements. Results: Our results show that both groups of materials (the nanomaterials and the medical devices) are not likely to cause any immunological adverse reaction and as a result might be characterized and selected as excellent candidates for medical applications. Conclusions: The effectiveness of the study is attributed to the measurement of a single factor in serum in order to acquire important information about the materials' properties e.g immunological response. The possibility to modify the above tested parameters during

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Differential effects of the complement peptides, C5a and C5a des Arg on human basophil and lung mast cell histamine release.

Cited by 100 publications

References 34 publications

Mast Cell Phenotype, Location, and Activation in Severe Asthma

Mast Cell Phenotype, Location, and Activation in Severe Asthma

Cloning, Expression, Cellular Distribution, and Role in Chemotaxis of a C5a Receptor in Rainbow Trout: The First Identification of a C5a Receptor in a Nonmammalian Species

IN-VITRO IMMUNOCOMPATIBILITY & CHARACTERIZATION AT NANOSCALE OF THIN FILMS AND VASCULAR MEDICAL DEVICES.

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