Mouse strains with typical mammalian levels of complement activity

Ong, Gaik Lin; Mattes, M. Jules

doi:10.1016/0022-1759(89)90088-4

Cited by 130 publications

(113 citation statements)

References 31 publications

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“…The mouse model is appropriate for the study of certain aspects of EHECinduced colonic and renal damage (5,12,18), low RBC counts and platelets (7,15), as well as toxin-induced complement activation in the kidney (16). Certain mouse strains, however, have a lower capacity to activate complement (52). Both mouse strains used in the present study were previously shown to have complement activity, which was higher in BALB/c mice than in C57BL/6 mice (52).…”

Section: Discussionmentioning

confidence: 86%

Early Terminal Complement Blockade and C6 Deficiency Are Protective in Enterohemorrhagic Escherichia coli–Infected Mice

Arvidsson

Rebetz

Loos

et al. 2016

The Journal of Immunology

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Complement activation occurs during enterohemorrhagic Escherichia coli (EHEC) infection and may exacerbate renal manifestations. In this study, we show glomerular C5b-9 deposits in the renal biopsy of a child with EHEC-associated hemolytic uremic syndrome. The role of the terminal complement complex, and its blockade as a therapeutic modality, was investigated in a mouse model of E. coli O157:H7 infection. BALB/c mice were treated with monoclonal anti-C5 i.p. on day 3 or 6 after intragastric inoculation and monitored for clinical signs of disease and weight loss for 14 d. All infected untreated mice (15 of 15) or those treated with an irrelevant Ab (8 of 8) developed severe illness. In contrast, only few infected mice treated with anti-C5 on day 3 developed symptoms (three of eight, p < 0.01 compared with mice treated with the irrelevant Ab on day 3) whereas most mice treated with anti-C5 on day 6 developed symptoms (six of eight). C6-deficient C57BL/6 mice were also inoculated with E. coli O157:H7 and only 1 of 14 developed disease, whereas 10 of 16 wild-type mice developed weight loss and severe disease (p < 0.01). Complement activation via the terminal pathway is thus involved in the development of disease in murine EHEC infection. Early blockade of the terminal complement pathway, before the development of symptoms, was largely protective, whereas late blockade was not. Likewise, lack of C6, and thereby deficient terminal complement complex, was protective in murine E. coli O157:H7 infection.

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Section: Discussionmentioning

confidence: 86%

Early Terminal Complement Blockade and C6 Deficiency Are Protective in Enterohemorrhagic Escherichia coli–Infected Mice

Arvidsson

Rebetz

Loos

et al. 2016

The Journal of Immunology

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“…In vitro, mouse C1 is less efficiently activated by fibrillar A␤ than is human C1, reportedly because of a difference in amino acid sequence in mouse versus human that interacts with A␤ and is involved in CCP activation (Webster et al, 1999). In addition, some laboratory strains of mice may have lower complement lytic activity than in human (Ong and Mattes, 1989). As a result, the effects of CCP activation in the human disease may have a greater contribution to neuropathology and neuronal cell injury than the transgenic mice models studied here, and thus inhibition of those events may result in even greater benefit in slowing the progression of pathology and cognitive dysfunction in AD.…”

Section: Discussionmentioning

confidence: 99%

Absence of C1q Leads to Less Neuropathology in Transgenic Mouse Models of Alzheimer's Disease

Fonseca¹,

Zhou²,

Botto³

et al. 2004

J. Neurosci.

287

248

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C1q, the recognition component of the classical complement activation pathway, is a multifunctional protein known to be expressed in brain of Alzheimer's disease (AD) patients. To experimentally address the role of C1q in AD, a mouse model lacking C1q (APPQϪ/Ϫ) was generated by crossing Tg2576 animals (APP) with C1q-deficient mice. The pathology of APPQϪ/Ϫ was compared with that of APP mice and B6SJL controls at 3-16 months of age by immunohistochemistry and Western blot analysis. At younger ages (3-6 months), when no plaque pathology was present, no significant differences were seen in any of the neuronal or glial markers tested. At older ages (9 -16 months), the APP and APPQϪ/Ϫ mice developed comparable total amyloid and fibrillar ␤-amyloid in frontal cortex and hippocampus; however, the level of activated glia surrounding the plaques was significantly lower in the APPQϪ/Ϫ mice at 12 and 16 months. In addition, although Tg2576 mice showed a progressive decrease in synaptophysin and MAP2 in the CA3 area of hippocampus compared with control B6SJL at 9, 12, and 16 months, the APPQϪ/Ϫ mice had significantly less of a decrease in these markers at 12 and 16 months. In a second murine model for AD containing transgenes for both APP and mutant presenilin 1 (APP/PS1), a similar reduction of pathology was seen in the APPPS1QϪ/Ϫ mice. These data suggest that at ages when the fibrillar plaque pathology is present, C1q exerts a detrimental effect on neuronal integrity, most likely through the activation of the classical complement cascade and the enhancement of inflammation.

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“…2B). Although common inbred strains of laboratory mice were known to have vanishingly low lytic complement activity (33,34), the relevance to murine models of microbial pathogenesis has not been widely appreciated. Our data suggest that for Leishmania and perhaps other pathogens, inbred mice may not be good models for probing the role of the lytic functions of complement relevant to human infectious diseases (in contrast to their utility in studying other aspects of the complement pathway) (8).…”

Section: Discussionmentioning

confidence: 99%

The role(s) of lipophosphoglycan (LPG) in the establishment ofLeishmania majorinfections in mammalian hosts

Späth

Garraway

Turco

et al. 2003

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

258

259

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The abundant cell surface glycolipid lipophosphoglycan (LPG) was implicated in many steps of the Leishmania infectious cycle by biochemical tests. The presence of other abundant surface or secreted glycoconjugates sharing LPG domains, however, has led to uncertainty about the relative contribution of LPG in vivo. Here we used an Leishmania major lpg1 ؊ mutant, which lacks LPG alone and shows attenuated virulence, to dissect the role of LPG in the establishment of macrophage infections in vivo. lpg1 ؊ was highly susceptible to human complement, had lost the ability to inhibit phagolysosomal fusion transiently, and was oxidant sensitive. Studies of mouse mutants defective in relevant defense mechanisms confirmed the role of LPG in oxidant resistance but called into question the importance of transient inhibition of phagolysosomal fusion for Leishmania macrophage survival. Moreover, the limited lytic activity of mouse complement appears to be an ineffective pathogen defense mechanism in vitro and in vivo, unlike human hosts. In contrast, lpg1 ؊ parasites bound C3b and resisted low pH and proteases normally, entered macrophages efficiently and silently, and continued to inhibit host-signaling pathways. These studies illustrate the value of mechanistic approaches focusing on both parasite and host defense pathways in dissecting the specific biological roles of complex virulence factors such as LPG.phosphoglycans ͉ trypanosomatid protozoan parasite ͉ oxidant resistance ͉ inhibition of macrophage activation ͉ adhesin

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Mouse strains with typical mammalian levels of complement activity

Cited by 130 publications

References 31 publications

Early Terminal Complement Blockade and C6 Deficiency Are Protective in Enterohemorrhagic Escherichia coli–Infected Mice

Early Terminal Complement Blockade and C6 Deficiency Are Protective in Enterohemorrhagic Escherichia coli–Infected Mice

Absence of C1q Leads to Less Neuropathology in Transgenic Mouse Models of Alzheimer's Disease

The role(s) of lipophosphoglycan (LPG) in the establishment ofLeishmania majorinfections in mammalian hosts

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