Degranulation from Human Eosinophils Stimulated with C3a and C5a

Takafuji, Shigeru; Tadokoro, Kenji; K, Ito; Dahinden, C. A.

doi:10.1159/000236743

Cited by 74 publications

(42 citation statements)

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“…Previous studies have shown that C3a can readily degranulate eosinophils, basophils, and mast cells (11,12) while also activating and modulating cytokine release from monocytes/macrophages (13). However, despite high expression of C3aR on neutrophils and a clear Ca 2+ mobilization response in response to C3a (or other C3aR ligands) (9,14), a clear role for C3a has not yet been ascribed to neutrophils (15), which form the vast majority of the granulocytic population.…”

mentioning

confidence: 99%

The receptor for complement component C3a mediates protection from intestinal ischemia-reperfusion injuries by inhibiting neutrophil mobilization

Brennan

Lynch

et al. 2013

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

138

158

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C3a is a key complement activation fragment, yet its neutrophil-expressed receptor (C3aR) still has no clearly defined role. In this study, we used a neutrophil-dependent mouse model of intestinal ischemia-reperfusion (IR) injury to explore the role of C3aR in acute tissue injuries. C3aR deficiency worsened intestinal injury, which corresponded with increased numbers of tissue-infiltrating neutrophils. Circulating neutrophils were significantly increased in C3aR −/− mice after intestinal ischemia, and C3aR −/− mice also mobilized more circulating neutrophils after granulocyte colony-stimulating factor infusion compared with WT mice, indicating a specific role for C3aR in constraining neutrophil mobilization in response to intestinal injury. In support of this role, C3aR −/− mice reconstituted with WT bone marrow reversed IR pathology back to WT levels. Complement C5a receptor (C5aR) antagonism in C3aR −/− mice also rectified the worsened pathology after intestinal IR injury but had no effect on circulating neutrophils, highlighting the opposing roles of C3a and C5a in disease pathogenesis. Finally, we found that using a potent C3a agonist to activate C3aR in vivo reduced neutrophil mobilization and ameliorated intestinal IR pathology in WT, but not C3aR −/− , mice. This study identifies a role for C3aR in regulating neutrophil mobilization after acute intestinal injury and highlights C3aR agonism as a potential treatment option for acute, neutrophil-driven pathologies.

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mentioning

confidence: 99%

The receptor for complement component C3a mediates protection from intestinal ischemia-reperfusion injuries by inhibiting neutrophil mobilization

Brennan

Lynch

et al. 2013

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

138

158

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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

193

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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“…glucoronidase [11], histamine [44] and eosinophil cationic protein (ECP) [17], stimulation of granulocyte and monocyte oxidative burst with the release of reactive oxygen species [12,13,45,46], an increased expression of b 2 -integrin adhesion molecules and shedding of L-selectin [14], an increase in vascular permeability [2,3] and delayed neutrophil apoptosis [16]. These mechanisms of C5a have been implicated in the induction of a potent inflammatory response and the prolongation of the life span of neutrophils in the presence of foreign antigens [16].…”

Section: Normal Pregnancymentioning

confidence: 99%

“…Its interaction with phagocytic cells increases oxidative burst [12,13], induces expression of adhesion molecules [14,15] and inhibits polymorphonuclear (PMN) apoptosis [16]. C3a effects are predominantly on mast cells and eosinophils, and include chemotaxis [10,11], granule release [11,17], expression of adhesion molecules (b 2 integrin) and L-selectin shedding [14]. C4a, the weakest anaphylatoxin [4], can only be generated through the classical pathway.…”

Section: Introductionmentioning

confidence: 99%

Increased concentration of the complement split product C5a in acute pyelonephritis during pregnancy

Soto

Richani

Romero

et al. 2005

The Journal of Maternal-Fetal & Neonatal Medicine

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Objective. Pregnant women with acute pyelonephritis develop acute respiratory distress syndrome (ARDS) more frequently than non-pregnant women. The reasons for this remain unknown. The complement system is a complex set of selfassembling proteins that have been implicated in the pathophysiology of ARDS and sepsis. The purpose of this study was to determine if activation of the complement system occurs in pregnant women with acute pyelonephritis. Methods. A cross-sectional study was conducted to determine the plasma concentrations of C3a, C4a and C5a (i.e., complement split products) in pregnant patients with acute pyelonephritis (n = 38) and normal pregnant women (n = 38). The complement split products C3a, C4a and C5a were measured using ELISA. Data were analyzed using non-parametric statistics. Results. 1) The median plasma concentration of C5a in pregnant patients with acute pyelonephritis was significantly higher than that in normal pregnant women (p 5 0.001); 2) there was no statistical difference in the median plasma concentration of C3a and C4a between the two groups (p 4 0.05); and 3) concentrations of C3a, C4a and C5a were not different among patients with acute pyelonephritis with and without bacteremia. Conclusions. 1) Pyelonephritis in pregnant women is associated with an increased plasma concentration of C5a, but not C3a and C4a; and 2) an excess of C5a can predispose pregnant women to develop ARDS and multi-organ failure in pyelonephritis. This finding may have clinical implications since blocking C5a improves ARDS in experimental sepsis.

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Degranulation from Human Eosinophils Stimulated with C3a and C5a

Cited by 74 publications

References 1 publication

The receptor for complement component C3a mediates protection from intestinal ischemia-reperfusion injuries by inhibiting neutrophil mobilization

The receptor for complement component C3a mediates protection from intestinal ischemia-reperfusion injuries by inhibiting neutrophil mobilization

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

Increased concentration of the complement split product C5a in acute pyelonephritis during pregnancy

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