C3a activates reactive oxygen radical species production and intracellular calcium transients in human eosinophils

Elsner, Jörn; Oppermann, Martin; Czech, Wolfgang; Dobos, Gustav; Schöpf, Erwin; Norgauer, Johannes; Kapp, Alexander

doi:10.1002/eji.1830240304

Cited by 150 publications

(112 citation statements)

References 27 publications

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“…Thus, activation of C3 in the fluid phase followed by rapid degradation of the C3b-like molecule by fI and fH (either in solution or bound to the bacterial surface through ligands, such as fHbp and NspA) could constitute a mechanism of complement escape. The C3a molecule produced by C3 convertase is one of the anaphylatoxins of the complement system and has diverse effects ranging from the release of histamine from human mast cells to chemotaxis of basophils and eosinophils to activation of neutrophils (34)(35)(36)(37). The activity of C3a in the bloodstream and tissues is tightly controlled by carboxypeptidases, which rapidly remove the Cterminal Arg residue (38,39).…”

Section: Discussionmentioning

confidence: 99%

Neisseria meningitidis NalP cleaves human complement C3, facilitating degradation of C3b and survival in human serum

Tordello

Vacca

Ram

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The complement system is a crucial component of the innate immune response against invading bacterial pathogens. The human pathogen Neisseria meningitidis (Nm) is known to possess several mechanisms to evade the complement system, including binding to complement inhibitors. In this study, we describe an additional mechanism used by Nm to evade the complement system and survive in human blood. Using an isogenic NalP deletion mutant and NalP complementing strains, we show that the autotransporter protease NalP cleaves C3, the central component of the complement cascade. The cleavage occurs 4 aa upstream from the natural C3 cleavage site and produces shorter C3a-like and longer C3b-like fragments. The C3b-like fragment is degraded in the presence of the complement regulators (factors H and I), and this degradation results in lower deposition of C3b on the bacterial surface. We conclude that NalP is an important factor to increase the survival of Nm in human serum.serum resistance | immune evasion

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Section: Discussionmentioning

confidence: 99%

Neisseria meningitidis NalP cleaves human complement C3, facilitating degradation of C3b and survival in human serum

Tordello

Vacca

Ram

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Cell Isolation-Human granulocytes were isolated from heparinanticoagulated venous blood from non-atopic healthy donors using Ficoll (Amersham Pharmacia Biotech) density gradient centrifugation as described previously (24). For further purification, granulocytes were resuspended in HEPES-buffered Hanks' balanced salt solution (HBSS; Life Technologies, Inc.), pH 7.4, containing 1 mg/ml BSA (HBSSϩBSA).…”

Section: Chemokines and Chemokine Receptor Antagonists-met-rantesmentioning

confidence: 99%

“…For further purification, granulocytes were resuspended in HEPES-buffered Hanks' balanced salt solution (HBSS; Life Technologies, Inc.), pH 7.4, containing 1 mg/ml BSA (HBSSϩBSA). Eosinophils were purified by negative selection with Dynabeads M-450 (Dynal, Hamburg, Germany) coated with anti-CD16 antibody (clone 3G8, Dianova, Hamburg, Germany) as described previously (24). The resulting eosinophil purity was 99.5%, as determined by microscopic examination with Kimura staining and flow cytometric analysis (FACScan ® , Becton Dickinson, Heidelberg, Germany) using phycoerythrinconjugated anti-CD16 antibody (clone 3G8, Dianova, Hamburg, Germany) (24).…”

Section: Chemokines and Chemokine Receptor Antagonists-met-rantesmentioning

confidence: 99%

Differential Activation of CC Chemokine Receptors by AOP-RANTES

Elsner¹,

Mack²,

Brühl³

et al. 2000

Journal of Biological Chemistry

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RANTES (regulated on activation normal T cell expressed) has been found at elevated levels in biological fluids from patients with a wide range of allergic and autoimmune diseases and is able to attract several subtypes of leukocytes including eosinophils and monocytes into inflamed tissue. Amino-terminal modifications of RANTES produce receptor antagonists which are candidates for blocking this cellular recruitment. Met-RANTES has been shown to modulate inflammation in vivo, while AOP-RANTES is a potent inhibitor of R5 human immunodeficiency virus type 1 (HIV-1) strains and has been shown to down-modulate CCR5 and prevent recycling of the receptor. We have studied the effect of AOP-RANTES in eosinophil activation and have found that it is able to efficiently elicit eosinophil effector functions through CCR3, as measured by the release of reactive oxygen species and calcium mobilization, whereas Met-RANTES is inactive in these assays. AOP-RANTES is found to inhibit CCR3-mediated HIV-1 infection with moderate potency, in contrast to its potent inhibition of CCR5-mediated HIV-1 infection. Furthermore, we have investigated the abilities of these modified proteins to down-modulate CCR1 and CCR3 from the surface of monocytes and eosinophils. We show here that AOP-RANTES is much less effective than RANTES in down-modulation of CCR1. Surprisingly, recycling of CCR1 was minimal after incubation with RANTES while there was complete recycling with AOP-RANTES. In the case of CCR3, no significant difference was found between RANTES and AOP-RANTES in down-modulation and recycling. It therefore appears that trafficking of RANTES receptors follows different patterns, which opens up potential new targets for therapeutic intervention.Chemokines are chemotactic proteins that play a central role in immune and inflammatory responses by the attraction and activation of leukocytes. They can be divided into two major classes on the basis of the arrangement of the amino acid cysteine in the amino-terminal region: the CXC and CC chemokines, and two minor subclasses, each comprising a single member, the C and CX3C subclasses (1-3). Initially, it was generally accepted that the chemokine subclasses differ in their biological activity to stimulate different kinds of leukocytes, so that CXC chemokines are mediators of acute inflammation through neutrophil activation while the CC chemokines mediate chronic inflammation by attracting leukocytes such as eosinophils, monocytes, lymphocytes, basophils, and dendritic cells. However, this paradigm has recently been shown to have exceptions; for example, CXCR3 is expressed on activated T cells (4) and neutrophils can be activated by CC chemokines following stimulation with interferon-␥ (5).Chemokines mediate their effects by binding to cell-surface receptors that belong to the seven-transmembrane domain G protein-coupled receptor superfamily (1). More recently, chemokine receptors have been subject to intense scrutiny following the discovery that several of them are co-receptors for HIV 1 cell entr...

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“…3 and 5). In addition, C3a and C5a can stimulate respiratory burst in macrophages (6,7), neutrophils (8,9), and eosinophils (10); stimulate the release of histamine from basophils (11,12) and mast cells (13,14); and regulate the synthesis of eosinophil cationic protein and adhesion to endothelial cells by eosinophils (15)(16)(17). C3a can also stimulate serotonin release from platelets (18) and modulate synthesis of IL-6 and TNF-␣ by B lymphocytes and monocytes (19,20).…”

mentioning

confidence: 99%

Expression of the Complement Anaphylatoxin C3a and C5a Receptors on Bronchial Epithelial and Smooth Muscle Cells in Models of Sepsis and Asthma

Drouin¹,

Kildsgaard²,

Haviland³

et al. 2001

The Journal of Immunology

192

149

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The presence of the complement-derived anaphylatoxin peptides, C3a and C5a, in the lung can induce respiratory distress characterized by contraction of the smooth muscle walls in bronchioles and pulmonary arteries and aggregation of platelets and leukocytes in pulmonary vessels. C3a and C5a mediate these effects by binding to their specific receptors, C3aR and C5aR, respectively. The cells that express these receptors in the lung have not been thoroughly investigated, nor has their expression been examined during inflammation. Accordingly, C3aR and C5aR expression in normal human and murine lung was determined in this study by immunohistochemistry and in situ hybridization. In addition, the expression of these receptors was delineated in mice subjected to LPS- and OVA-induced models of inflammation. Under noninflamed conditions, C3aR and C5aR protein and mRNA were expressed by bronchial epithelial and smooth muscle cells of both human and mouse lung. C3aR expression increased significantly on both bronchial epithelial and smooth muscle cells in mice treated with LPS; however, in the OVA-challenged animals only the bronchial smooth muscle cells showed increased C3aR expression. C5aR expression also increased significantly on bronchial epithelial cells in mice treated with LPS, but was not elevated in either cell type in the OVA-challenged mice. These results demonstrate the expression of C3aR and C5aR by cells endogenous to the lung, and, given the participation of bronchial epithelial and smooth muscle cells in the pathology of diseases such as sepsis and asthma, the data suggest a role for these receptors during lung inflammation.

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C3a activates reactive oxygen radical species production and intracellular calcium transients in human eosinophils

Cited by 150 publications

References 27 publications

Neisseria meningitidis NalP cleaves human complement C3, facilitating degradation of C3b and survival in human serum

Neisseria meningitidis NalP cleaves human complement C3, facilitating degradation of C3b and survival in human serum

Differential Activation of CC Chemokine Receptors by AOP-RANTES

Expression of the Complement Anaphylatoxin C3a and C5a Receptors on Bronchial Epithelial and Smooth Muscle Cells in Models of Sepsis and Asthma

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