Regulation of mast cell activation by complement-derived peptides

Erdei, Anna; Andrásfalvy, Márton; Péterfy, Hajna; Tóth, Gábor; Pecht, Israel

doi:10.1016/j.imlet.2003.11.019

Cited by 44 publications

(31 citation statements)

References 19 publications

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“…The lectin pathway may also be activated by translocation of microbial products from the gut, a process that is postulated to occur during exercise (38) or other events such as infection, injury, or vaccine and trigger local inflammation and a variety of autoimmune diseases (39). Either situation may lead to increased C4a in CFS subjects compared with controls, and this C4a may have a regulatory role in inflammation by inhibiting monocyte chemotaxis (40) or through functions similar to C3a "activator and inhibitor" sequences as proposed by Erdei et al (2004) (41). An antiinflammatory role would coincide with the downregulation of MASP2 expression in control subjects that occurred 1 hour postexercise.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Control of Complement Activation in an Exercise Model of Chronic Fatigue Syndrome

Sorensen

Jones

Vernon

et al. 2009

Mol Med

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Complement activation resulting in significant increases of C4a split product may be a marker of postexertional malaise in individuals with chronic fatigue syndrome (CFS). This study focused on identification of the transcriptional control that may contribute to the increased C4a in CFS subjects after exercise. We used quantitative reverse-transcription polymerase chain reaction to evaluate differential expression of genes in the classical and lectin pathways in peripheral blood mononuclear cells (PBMCs). Calibrated expression values were normalized to the internal reference gene peptidylpropyl isomerase B (PPIB), the external reference gene ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL), or the geometric mean (GM) of the genes ribosomal protein, large, P0 (RPLP0) and phosphoglycerate kinase 1 (PGK1). All nine genes tested, except mannose-binding lectin 2 (MBL2), were expressed in PBMCs. At 1 hour postexercise, C4, mannan-binding lectin serine protease 2 (MASP2) and ficolin 1 (FCN1) transcripts were detected at higher levels (≥2-fold) in at least 50% (4 of 8) of CFS subjects and were detected in 88% (7 of 8) CFS subjects when subjects with overexpression of either C4 or MASP2 were combined. Only an increase in the MASP2 transcript was statistically significant (PPIB, P = 0.001; GM, P = 0.047; rbcL, P = 0.045). This result may be due to the significant but transient downregulation of MASP2 in control subjects (PPIB, P = 0.023; rbcL, P = 0.027). By 6 hours postexercise, MASP2 expression was similar in both groups. In conclusion, lectin pathway responded to exercise differentially in CFS than in control subjects. MASP2 downregulation may act as an antiinflammatory acute-phase response in healthy subjects, whereas its elevated level may account for increased C4a and inflammation-mediated postexertional malaise in CFS subjects.

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Section: Discussionmentioning

confidence: 99%

Transcriptional Control of Complement Activation in an Exercise Model of Chronic Fatigue Syndrome

Sorensen

Jones

Vernon

et al. 2009

Mol Med

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“…It has been suggested that C3a binding to C3a receptor inhibits FceRI signaling in some mast cells. This process requires a sequence in C3a, distinct from the C3a receptor binding region, and directly inhibits FceRI b subunit phosphorylation and subsequent signaling events [63,64]. Mast cell contact with airway smooth muscle cells enhances C3a receptor mediated mast cell degranulation [65], suggesting that in vitro studies with isolated mast cells might underestimate the in vivo importance of these pathways.…”

Section: Complement Pathway Interactions With Mast Cellsmentioning

confidence: 99%

New and emerging roles for mast cells in host defence

Dawicki

Marshall

2007

Current Opinion in Immunology

250

226

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“…Surprisingly, the role of C3a in mast cell activation remains controversial and appears to depend on the mast cells subtype. For example, murine bone marrow-derived mast cells and a rat basophilic leukemia, RBL-2H3 cells, which have been used extensively as mast cell models, do not express C3a receptors [37]. In contrast, C3a receptors are expressed in human CD34 + -derived primary mast cell cultures [38,39], human mast cell lines HMC-1 [40,41] and LAD 2 [39] as well as murine pulmonary mast cells (Thangam, B and Ali, H, unpublished data).…”

Section: Relationship Between C3ar and Fcεri In Mast Cell Activation mentioning

confidence: 99%

Anaphylatoxin C3a receptors in asthma

Ali

Panettieri

2005

Respir Res

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The complement system forms the central core of innate immunity but also mediates a variety of inflammatory responses. Anaphylatoxin C3a, which is generated as a byproduct of complement activation, has long been known to activate mast cells, basophils and eosinophils and to cause smooth muscle contraction. However, the role of C3a in the pathogenesis of allergic asthma remains unclear. In this review, we examine the role of C3a in promoting asthma. Following allergen challenge, C3a is generated in the lung of subjects with asthma but not healthy subjects. Furthermore, deficiency in C3a generation or in G protein coupled receptor for C3a abrogates allergen-induced responses in murine models of pulmonary inflammation and airway hyperresponsiveness. In addition, inhibition of complement activation or administration of small molecule inhibitors of C3a receptor after sensitization but before allergen challenge inhibits airway responses. At a cellular level, C3a stimulates robust mast cell degranulation that is greatly enhanced following cell-cell contact with airway smooth muscle (ASM) cells. Therefore, C3a likely plays an important role in asthma primarily by regulating mast cell-ASM cell interaction.

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Regulation of mast cell activation by complement-derived peptides

Cited by 44 publications

References 19 publications

Transcriptional Control of Complement Activation in an Exercise Model of Chronic Fatigue Syndrome

Transcriptional Control of Complement Activation in an Exercise Model of Chronic Fatigue Syndrome

New and emerging roles for mast cells in host defence

Anaphylatoxin C3a receptors in asthma

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