scholarly journals PEG-fDAO Reduces Lung Inflammation in Chronic Granulomatous Disease Mice Post Challenge With Nonviable Candida Albicans

Author(s):  
Hiroyuki Nunoi ◽  
Peiyu Xie ◽  
Hideaki Nakamura ◽  
Yasuaki Aratani ◽  
Jun Fang ◽  
...  

Abstract We previously reported that polyethylene glycol-conjugated recombinant porcine D-amino acid oxidase (PEG-pDAO) could supply reactive oxygen species (ROS) to defective NADPH oxidase in neutrophils of patients with chronic granulomatous disease (CGD), and neutrophils regain bactericidal activity in vitro. In the present study, we employed an in vivo nonviable Candida albicans (nCA)-induced lung inflammation model using gp91-phox knockout CGD mice and novel PEG conjugates of Fusarium spp. D-amino acid oxidase (PEG-fDAO), rather than PEG-pDAO. Using three experimentation strategies with the in vivo lung inflammation model, the mouse body weight, lung weight, and lung pathology were evaluated to confirm the efficacy of ROS-generating enzyme replacement therapy with PEG-fDAO. The lung weight and pathological findings were significantly ameliorated by the administration of PEG-fDAO followed by intraperitoneal injection of D-phenylalanine or D-proline. These data suggest that PEG- fDAO with the function of targeted delivery to the nCA-induced inflammation site is applicable in the treatment of inflammation in CGD in vivo.

2021 ◽  
Author(s):  
Hiroyuki Nunoi ◽  
Peiyu Xie ◽  
Hideaki Nakamura ◽  
Yasuaki Aratani ◽  
Jun Fang ◽  
...  

Abstract We previously reported that polyethylene glycol-conjugated recombinant porcine D-amino acid oxidase (PEG-pDAO) could supply reactive oxygen species (ROS) to defective NADPH oxidase in neutrophils of patients with chronic granulomatous disease (CGD), and neutrophils regain bactericidal activity in vitro. In the present study, we employed an in vivo nonviable Candida albicans (nCA)-induced lung inflammation model using gp91-phox knockout CGD mice and novel PEG conjugates of Fusarium spp. D-amino acid oxidase (PEG-fDAO), rather than PEG-pDAO. Using three experimentation strategies with the in vivo lung inflammation model, the mouse body weight, lung weight, and lung pathology were evaluated to confirm the efficacy of ROS-generating enzyme replacement therapy with PEG-fDAO. The lung weight and pathological findings were significantly ameliorated by the administration of PEG-fDAO followed by intraperitoneal injection of D-phenylalanine or D-proline. These data suggest that PEG- fDAO with the function of targeted delivery to the nCA-induced inflammation site is applicable in the treatment of inflammation in CGD in vivo.


2013 ◽  
Vol 1 (1) ◽  
Author(s):  
Seth C. Hopkins ◽  
Una C. Campbell ◽  
Michele L. R. Heffernan ◽  
Kerry L. Spear ◽  
Ross D. Jeggo ◽  
...  

2004 ◽  
Vol 287 (1) ◽  
pp. E160-E165 ◽  
Author(s):  
Hiroshi Hasegawa ◽  
Takehisa Matsukawa ◽  
Yoshihiko Shinohara ◽  
Ryuichi Konno ◽  
Takao Hashimoto

d-Amino acids are now recognized to be widely present in mammals. Renal d-amino-acid oxidase (DAO) is associated with conversion of d-amino acids to the corresponding α-keto acids, but its contribution in vivo is poorly understood because the α-keto acids and/or l-amino acids formed are indistinguishable from endogenous compounds. First, we examined whether DAO is indispensable for conversion of d-amino acids to their α-keto acids by using the stable isotope tracer technique. After a bolus intravenous administration of d-[2H7]leucine to mutant mice lacking DAO activity (ddY/DAO−) and normal mice (ddY/DAO+), elimination of d-[2H7]leucine and formation of α-[2H7]ketoisocaproic acid ([2H7]KIC) and l-[2H7]leucine in plasma were determined. The ddY/DAO− mice, in contrast to ddY/DAO+ mice, failed to convert d-[2H7]leucine to [2H7]KIC and l-[2H7]leucine. This result clearly revealed that DAO was indispensable for the process of chiral inversion of d-leucine. We further investigated the effect of renal mass reduction by partial nephrectomy on elimination of d-[2H7]leucine and formation of [2H7]KIC and l-[2H7]leucine. Renal mass reduction slowed down the elimination of d-[2H7]leucine. The fraction of conversion of d-[2H7]leucine to [2H7]KIC in sham-operated rats was 0.77, whereas that in five-sixths-nephrectomized rats was 0.25. The elimination behavior of d-[2H7]leucine observed in rats suggested that kidney was the principal organ responsible for converting d-leucine to KIC.


1979 ◽  
Vol 25 (6) ◽  
pp. 765-772 ◽  
Author(s):  
Sara E. Miller ◽  
W. R. Finnerty

From electron-microscopical observations, a decreased metabolic activity in 3-day-old Candida albicans chlamydospores was suggested, and progressive deterioration in chlamydospores aged 2–8 months was shown. Oxygen utilization by chlamydospore–pseudomycelium (CSP) preparations was less than that by yeast, while 3-day-old CSP preparations used significantly less O2 than 24-h CSP preparations. Amino acid incorporation was greater in yeast than in CSP preparations. Leucine incorporation by 20-h yeasts was twice that of 5-day yeasts and 5 times that of 20-h and 5-day CSP. Amino acid decarboxylation was similar in yeasts and CSP and was determined by end-product analyses to be via amino acid oxidase. Light microscopy autoradiography of [14C]leucine incorporation demonstrated that the metabolic activity in CSP preparations was due to the young growing tips of the pseudomycelium and not to mature chlamydospores. Yeasts did not take up trypan blue but could be stained if first autoclaved or treated with 10% acid or 10% base. Young chlamydospores grown in the presence of trypan blue developed unstained and became permeable to the dye at [Formula: see text] days. These data suggest that chlamydospores of C. albicans do not function in the classical role attributed to spores; i.e., mature chlamydospores cannot germinate, but rather age, deteriorate, and die.


2010 ◽  
Vol 25 (6) ◽  
pp. 1454-1459 ◽  
Author(s):  
Zainiharyati M. Zain ◽  
Robert D. O’Neill ◽  
John P. Lowry ◽  
Kenneth W. Pierce ◽  
Mark Tricklebank ◽  
...  

PLoS ONE ◽  
2017 ◽  
Vol 12 (12) ◽  
pp. e0188912 ◽  
Author(s):  
Nazanin Rahmani Kondori ◽  
Praveen Paul ◽  
Jacqueline P. Robbins ◽  
Ke Liu ◽  
John C. W. Hildyard ◽  
...  

2016 ◽  
Vol 91 (1) ◽  
pp. 427-437 ◽  
Author(s):  
Lisanne Luks ◽  
Silvia Sacchi ◽  
Loredano Pollegioni ◽  
Daniel R. Dietrich

2012 ◽  
Vol 80 (4) ◽  
pp. 1546-1553 ◽  
Author(s):  
Hideaki Nakamura ◽  
Jun Fang ◽  
Hiroshi Maeda

ABSTRACTd-Amino acid oxidase (DAO) is a hydrogen peroxide-generating enzyme that uses ad-amino acid as a substrate. We hypothesized that DAO may protect against bacterial infection, because hydrogen peroxide is one of the most important molecules in the antibacterial defense systems in mammals. We show here that DAO suppressed the growth ofStaphylococcus aureusin a manner that depended on the concentration of DAO andd-amino acidin vitro. Addition of catalase abolished the bacteriostatic activity of DAO. Although DAO plusd-Ala showed less bactericidal activity, addition of myeloperoxidase (MPO) greatly enhanced the bactericidal activity of DAO. Furthermore, DAO was able to utilize bacterial lysate, which containsd-Ala derived from peptidoglycan; this could produce hydrogen peroxide with, in the presence of myeloperoxidase, formation of hypochlorous acid. This concerted reaction of DAO and MPO led to the bactericidal action.In vivoexperiments showed that DAO−/−(mutant) mice were more susceptible toS. aureusinfection than were DAO+/+(wild-type) mice. These results suggest that DAO, together with myeloperoxidase, may play an important role in antibacterial systems in mammals.


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