Inactivation of the complement anaphylatoxin C5a by secreted products of parasitic nematodes

Rees-Roberts, Dominic; Mullen, Lisa; Gounaris, Kleoniki; Selkirk, Murray E.

doi:10.1016/j.ijpara.2009.10.006

Cited by 22 publications

(15 citation statements)

References 48 publications

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“…Brugia malayi and Trichinella spiralis, parasitic nematodes, release a metallocarboxypeptidase that inactivates C5a (Rees-Roberts et al, 2010), presumably to prevent eosinophil chemotaxis and activation. Streptococcus pyogenes produces a C5a peptidase (Wexler et al, 1985) that cleaves between His67 and Lys68 (Cleary et al, 1992).…”

Section: Deactivation Of Complement Peptidesmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. LXXXVII. Complement Peptide C5a, C4a, and C3a Receptors

Klos

Wende²,

Wareham³

et al. 2013

Pharmacol Rev

232

245

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Section: Deactivation Of Complement Peptidesmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. LXXXVII. Complement Peptide C5a, C4a, and C3a Receptors

Klos

Wende²,

Wareham³

et al. 2013

Pharmacol Rev

232

245

View full text Add to dashboard Cite

“…However, Mf presence did down-regulate mRNA expression of the inflammatory complement component, C5, in HUVEC and HLMVEC. In light of the recent report, that B. malayi Mf secrete a C5a-cleaving serine protease, this suggests that C5 products may be potentially damaging to filarial nematodes [27]. Similarly, mRNA expression of CCL23, a chemoattractant for monocytes, neutrophils and T cells, was downregulated in HLMVEC.…”

Section: Discussionmentioning

confidence: 82%

“…In addition, the proportion of macrophages within these leukocyte populations was significantly lower in Mf implanted rather than adult implanted mice [26]. Previous work has also shown that a serine protease derived from B. malayi Mf abolishes C5a-mediated chemotaxis of granulocytes [27]. Furthermore both adult B. malayi and Mf extracts inhibit hyper-permeability induced by TNF-α or IL-1α, of lymphatic EC monolayers to dextran.…”

Section: Discussionmentioning

confidence: 86%

Live Brugia malayi Microfilariae Inhibit Transendothelial Migration of Neutrophils and Monocytes

et al. 2012

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Lymphatic filariasis is a major tropical disease caused by the parasite Brugia malayi. Microfilariae (Mf) circulate in the peripheral blood for 2–3 hours in synchronisation with maximal feeding of the mosquito vector. When absent from the peripheral blood, Mf sequester in the capillaries of the lungs. Mf are therefore in close contact with vascular endothelial cells (EC) and may induce EC immune function and/or wound repair mechanisms such as angiogenesis. In this study, Mf were co-cultured with human umbilical vein EC (HUVEC) or human lung microvascular EC (HLMVEC) and the transendothelial migration of leukocyte subsets was analysed. In addition, the protein and/or mRNA expression of chemokine, cytokine and angiogenic mediators in endothelial cells in the presence of live microfilariae were measured by a combination of cDNA arrays, protein arrays, ELISA and fluorescence antibody tests.Surprisingly, our findings indicate that Mf presence partially blocked transendothelial migration of monocytes and neutrophils, but not lymphocytes. However, Mf exposure did not result in altered vascular EC expression of key mediators of the tethering stage of extravasation, such as ICAM-1, VCAM-1 and various chemokines. To further analyse the immunological function of vascular EC in the presence of Mf, we measured the mRNA and/or protein expression of a number of pro-inflammatory mediators. We found that expression levels of the mediators tested were predominantly unaltered upon B. malayi Mf exposure. In addition, a comparison of angiogenic mediators induced by intact Mf and Wolbachia-depleted Mf revealed that even intact Mf induce the expression of remarkably few angiogenic mediators in vascular EC. Our study suggests that live microfilariae are remarkably inert in their induction and/or activation of vascular cells in their immediate local environment. Overall, this work presents important insights into the immunological function of the vascular endothelium during an infection with B. malayi.

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“…through their surface receptors binding to these byproducts. For instance, the small fragment byproducts such as C5a, an anaphylatoxins, also play an important role in inflammation and especially in host defense against parasites (Rees-Roberts et al, 2010) (Mosser and Brittingham, 1997). These anaphylatoxins can cause mast cell and basophil degranulation, with the release of histamine and other substances that increase vascular permeability and stimulate smooth muscle constriction.…”

Section: Complement Activation and Complement Regulationmentioning

confidence: 99%

Complement and HIV-I infection/HIV-associated neurocognitive disorders

et al. 2014

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The various neurological complications associated with HIV-1 infection, specifically HIV-associated neurocognitive disorders (HAND) persist as a major public health burden worldwide. Despite the widespread use of anti-retroviral therapy, the prevalence of HAND is significantly high. HAND results from the direct effects of an HIV-1 infection as well as secondary effects of HIV-1-induced immune reaction and inflammatory response. Complement, a critical mediator of innate and acquired immunity, plays important roles in defeating many viral infections by the formation of a lytic pore or indirectly by opsonization and recruitment of phagocytes. While the role of complement in the pathogenesis of HIV-1 infection and HAND has been previously recognized for over fifteen years, it has been largely underestimated thus far. Complement can be activated through HIV-1 envelope proteins, mannose binding lectins (MBL) and anti-HIV-1 antibodies. Complement not only fights against HIV-1 infection but also enhances HIV-1 infection. Also, HIV-1 can hijack complement regulators such as CD59 and CD55 and can utilize these regulators and factor H to escape from complement attack. Normally, complement levels in brain are much lower than plasma levels and there is no or little complement deposition in brain cells. Interestingly, local production and deposition of complement are dramatically increased in HIV-1-infected brain, indicating that complement may contribute to the pathogenesis of HAND. Here, we review the current understanding of the role of complement in HIV-1 infection and HAND as well as potential therapeutic approaches targeting to the complement system for the treatment and eradications of HIV-1 infection.

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Inactivation of the complement anaphylatoxin C5a by secreted products of parasitic nematodes

Abstract: Graphical abstract

Cited by 22 publications

References 48 publications

International Union of Basic and Clinical Pharmacology. LXXXVII. Complement Peptide C5a, C4a, and C3a Receptors

International Union of Basic and Clinical Pharmacology. LXXXVII. Complement Peptide C5a, C4a, and C3a Receptors

Live Brugia malayi Microfilariae Inhibit Transendothelial Migration of Neutrophils and Monocytes

Complement and HIV-I infection/HIV-associated neurocognitive disorders

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