Essential Role of Factor B of the Alternative Complement Pathway in Complement Activation and Opsonophagocytosis during Acute Pneumococcal Otitis Media in Mice

Li, Qian; Li, Yong Xing; Stahl, Gregory L.; Thurman, Joshua M.; He, Yujuan; Tong, Hua Hua

doi:10.1128/iai.00168-11

Cited by 32 publications

(39 citation statements)

References 31 publications

(35 reference statements)

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“…Using 24-h urine samples, the UNGAL concentration was examined by a mouse NGAL ELISA kit ® (Cedarlane, Burlington, NC, USA) (33). UAlb excretion and UAGT excretion were measured using mouse albumin ELISA ® (Immunology Consultants Laboratory, Inc., Newberg, OR, USA) (34) and the mouse total angiotensinogen assay kit ® (Immuno-Biological Laboratories Co., Ltd., Takasaki) (21), respectively. The ratio of UAGT to UAlb (UAGT/UAlb) was calculated using each data set (ng·µg −1 ).…”

Section: Methodsmentioning

confidence: 99%

Urinary Angiotensinogen as a Novel Early Biomarker of Intrarenal Renin^|^ndash;Angiotensin System Activation in Experimental Type 1 Diabetes

2012

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Urinary excretion of albumin (UAlb) is used clinically as a marker of diabetic nephropathy (DN). Although DN was thought to be a unidirectional process, recent studies demonstrated that a large proportion of patients diagnosed with DN reverted to normoalbuminuria. Moreover, despite the normoalbuminuria, one-third of them exhibited reduced renal function even during the microalbuminuric stage. This study was performed to investigate whether urinary angiotensinogen (UAGT) level may serve as a useful marker of the early stage of experimental type 1 diabetes (T1DM). T1DM was induced by a single intraperitoneal injection of streptozotocin. Control mice were injected with citrate buffer. Two days after streptozotocin injection, half of the mice received continuous insulin treatment. Our data showed that UAlb excretion was increased 6 days after streptozotocin injection compared to controls, whereas UAGT excretion was increased at an earlier time point. These increases were reversed by insulin treatment. The UAGT to UAlb ratio was increased in diabetic mice compared to control mice. Furthermore, the increased AGT expression in the kidneys was observed in diabetic mice. These data suggest that UAGT might be useful as a novel early biomarker of activation of the renin–angiotensin system in experimental type 1 diabetes.

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Section: Methodsmentioning

confidence: 99%

Urinary Angiotensinogen as a Novel Early Biomarker of Intrarenal Renin^|^ndash;Angiotensin System Activation in Experimental Type 1 Diabetes

2012

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“…The wild-type (WT) Streptococcus pneumoniae strains type 6A (EF3114) (2,24) and D39 (type 2) (23) and their corresponding mutants were grown routinely at 37°C in Todd-Hewitt broth (Difco) supplemented with 0.5% (wt/vol) yeast extract (THY). For transformation experiments, cells were grown in chemically defined medium (21) with 0.5% yeast extract (CϩY).…”

Section: Methodsmentioning

confidence: 99%

Strain-Specific Regulatory Role of Eukaryote-Like Serine/Threonine Phosphatase in Pneumococcal Adherence

Agarwal

Pancholi

2012

Infect Immun

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ABSTRACTStreptococcus pneumoniaeexploits a battery of virulence factors to colonize the host. Although the eukaryote-like Ser/Thr kinase ofS. pneumoniae(StkP) has been implicated in physiology and virulence, the role of its cotranscribing phosphatase (PhpP) has remained elusive. The construction of nonpolar markerlessphpPknockout mutants (ΔphpP) in two pathogenic strains, D39 (type 2) and 6A-EF3114 (type 6A), indicated that PhpP is not indispensable for pneumococcal survival. Further, PhpP also participates in the regulation of cell wall biosynthesis/division, adherence, and biofilm formation in a strain-specific manner. Additionally, we provide hitherto-unknownin vitroandin vivoevidence of a physiologically relevant biochemical link between the StkP/PhpP-mediated cognate regulation and the two-component regulatory system TCS06 (RR06/HK06) that regulates the expression of the gene encoding an important pneumococcal surface adhesin, CbpA, which was found to be significantly upregulated in ΔphpPmutants. In particular, StkP (threonine)-phosphorylated RR06 bound to thecbpApromoter with high efficiency even in the absence of the HK06-responsive and catalytically active aspartate 51 residue. Together, our findings unravel the significant contributions of PhpP in pneumococcal physiology and adherence.

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“…We have previously shown that AP activation mediates opsonophagocytosis of the bacteria in this model (22). In vitro , more C3b was deposited on S. pneumoniae incubated with either normal human or murine serum when annexin A2 was added to the reaction (Figures 12A and B), demonstrating that annexin A2 can also increase complement activation on the surface of bacteria.…”

Section: Resultsmentioning

confidence: 66%

“…Acute otitis media was then induced by direct bilateral transtympanical inoculation with approximately 1 × 10 3 colony forming units (CFU) of opaque or transparent Streptococcus pneumoniae (Spn) in sterile pyrogen-free saline as previously described (21, 22). Mice were anesthetized and sacrificed 24 or 48 hours post inoculation.…”

Section: Methodsmentioning

confidence: 99%

Annexin A2 Enhances Complement Activation by Inhibiting Factor H

Renner

Tong

Laskowski

et al. 2016

The Journal of Immunology

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Factor H is a circulating protein that regulates activation of the alternative pathway (AP) of complement. Mutations and genetic variations of factor H are associated with several AP-mediated diseases, highlighting the critical role of factor H in AP regulation. AP-mediated inflammation is typically triggered by illness or tissue injury, however, and tissue injury can trigger AP activation in individuals with fully functional factor H. This suggests that factor H function is affected by local conditions within tissues. We hypothesized that inducible proteins impair the ability of factor H to locally control the AP, thereby increasing AP activation. We used purified murine factor H to immunoprecipitate binding partners from mouse kidneys. Using immunoaffinity liquid chromatography-mass spectrometry we then identified annexin A2 as a factor H binding partner. Further experiments showed that annexin A2 reduces the binding of factor H to cell surfaces. Recombinant annexin A2 impaired complement regulation by factor H, and increased complement activation on renal cell surfaces in vitro and in vivo. In a murine model of acute pneumococcal otitis media the administration of annexin A2 increased AP-mediated bacterial opsonization and clearance. In conclusion, the local production of annexin A2 within tissues suppresses regulation of the AP by factor H. Annexin A2 can contribute to AP-mediated tissue inflammation by locally impairing factor H function, but annexin A2 can also improve complement-mediated bacterial clearance.

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Essential Role of Factor B of the Alternative Complement Pathway in Complement Activation and Opsonophagocytosis during Acute Pneumococcal Otitis Media in Mice

Cited by 32 publications

References 31 publications

Urinary Angiotensinogen as a Novel Early Biomarker of Intrarenal Renin^|^ndash;Angiotensin System Activation in Experimental Type 1 Diabetes

Urinary Angiotensinogen as a Novel Early Biomarker of Intrarenal Renin^|^ndash;Angiotensin System Activation in Experimental Type 1 Diabetes

Strain-Specific Regulatory Role of Eukaryote-Like Serine/Threonine Phosphatase in Pneumococcal Adherence

Annexin A2 Enhances Complement Activation by Inhibiting Factor H

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