Chemotactic and Anaphylatoxic Fragment Cleaved from the Fifth Component of Guinea Pig Complement

Shin, Hyunjung; Snyderman, Ralph; Friedman, Eileen; Mellors, Alice; Mayer, Manfred M.

doi:10.1126/science.162.3851.361

Cited by 262 publications

(97 citation statements)

References 13 publications

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“…C5a, the most potent anaphylatoxin, can induce oxidative burst in neutrophils and stimulate oxygen radical species production [49][50][51], enhance phagocytosis [49], chemoattract granulocytes [7,52], and reduce neutrophil apoptosis [53]. Interestingly, these findings have been described in normal pregnant women [26,27,54].…”

Section: Discussionmentioning

confidence: 77%

Normal pregnancy is characterized by systemic activation of the complement system

Richani

Soto

Romero

et al. 2005

The Journal of Maternal-Fetal & Neonatal Medicine

177

123

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Background. The complement system, a major component of innate immunity, has recently been implicated in the mechanisms of fetal loss and placental inflammation in the anti-phospholipid antibody syndrome. Inhibition of complement has been proposed as an absolute requirement for normal pregnancy. Yet, pregnancy is characterized by a generalized activation of the innate immune system. This study was conducted to determine whether or not normal pregnancy is associated with complement activation in the maternal circulation. Methods. Anaphylatoxins (C3a, C4a and C5a) were determined in the plasma of normal pregnant (20-42 wks; n = 134) and non-pregnant women (n = 40). These complement split products (C3a, C4a and C5a) were measured using specific immunoassays. Non-parametric statistics were used for analysis. Results. 1) The median plasma concentrations of C3a, C4a and C5a were significantly higher in normal pregnant women than in non-pregnant women (all p 5 0.001); 2) the concentration of C3a, C4a and C5a did not change with gestational age (p 4 0.05); and 3) the median plasma concentration of C3a had a positive correlation with the plasma C4a and C5a concentrations (r = 0.36, p 5 0.001 and r = 0.35, p 5 0.001, respectively). Conclusion. 1) Normal human pregnancy is associated with evidence of complement activation, as determined by higher concentrations of the anaphylatoxins C3a, C4a and C5a in the maternal circulation; and 2) we propose that physiologic activation of the complement system during pregnancy is a compensatory mechanism aimed at protecting the host against infection.

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Section: Discussionmentioning

confidence: 77%

Normal pregnancy is characterized by systemic activation of the complement system

Richani

Soto

Romero

et al. 2005

The Journal of Maternal-Fetal & Neonatal Medicine

177

123

View full text Add to dashboard Cite

show abstract

“…Besides its strong chemotactic activity, other effects of C5a are known: release from phagocytic cells of granular enzymes, production in neutrophils of superoxide anion, histamine release from mast cells, vasodilatation, increased vascular permeability, smooth muscle contraction, and induction of thymocyte apoptosis during sepsis (3,(6)(7)(8)(9)(10). The responses to C5a are mediated by a pertussis toxin-sensitive G protein-linked seven-transmembrane C5a receptor (C5aR), which belongs to the superfamily of rhodopsin-type receptors (11,12).…”

Section: Introductionmentioning

confidence: 99%

INCREASED C5a RECEPTOR EXPRESSION IN SEPSIS.

Riedemann¹,

Guo²,

Neff³

et al. 2002

Shock

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“…In contrast to bacterial pathogens, it is unlikely that formation of the membrane-attack complex C5b-C9 contributes to C. albicans killing (11). Among complement activation products, the anaphylatoxin C5a, generated by cleavage of C5 by a C5 convertase mediates a broad range of proinflammatory effects: it is a strong chemoattractant for neutrophils as well as monocytes and increases PMN effector functions (oxidative burst, phagocytosis, and degranulation) (14)(15)(16). Elevated plasma levels of C5a are found in sepsis patients.…”

mentioning

confidence: 99%

A Second Stimulus Required for Enhanced Antifungal Activity of Human Neutrophils in Blood Is Provided by Anaphylatoxin C5a

Hünniger

Bieber

Martin

et al. 2015

The Journal of Immunology

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Polymorphonuclear neutrophilic granulocytes (PMN) as cellular components of innate immunity play a crucial role in the defense against systemic Candida albicans infection. To analyze stimuli that are required for PMN activity during C. albicans infection in a situation similar to in vivo, we used a human whole-blood infection model. In this model, PMN activation 10 min after C. albicans infection was largely dependent on the anaphylatoxin C5a. Most importantly, C5a enabled blood PMN to overcome filament-restricted recognition of C. albicans and allowed efficient elimination of nonfilamentous C. albicans cph1Δ/efg1Δ from blood. Major PMN effector mechanisms, including oxidative burst, release of secondary granule contents and initial fungal phagocytosis could be prevented by blocking C5a receptor signaling. Identical effects were achieved using a humanized Ab specifically targeting human C5a. Phagocytosis of C. albicans 10 min postinfection was mediated by C5a-dependent enhancement of CD11b surface expression on PMN, thus establishing the C5a-C5aR-CD11b axis as a major modulator of early anti-Candida immune responses in human blood. In contrast, phagocytosis of C. albicans by PMN 60 min postinfection occurred almost independently of C5a and mainly contributed to activation of phagocytically active PMN at later time points. Our results show that C5a is a critical mediator in human blood during C. albicans infection.

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Chemotactic and Anaphylatoxic Fragment Cleaved from the Fifth Component of Guinea Pig Complement

Cited by 262 publications

References 13 publications

Normal pregnancy is characterized by systemic activation of the complement system

Normal pregnancy is characterized by systemic activation of the complement system

INCREASED C5a RECEPTOR EXPRESSION IN SEPSIS.

A Second Stimulus Required for Enhanced Antifungal Activity of Human Neutrophils in Blood Is Provided by Anaphylatoxin C5a

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