Positron emission tomography with [18F]fluorodeoxyglucose to evaluate neutrophil kinetics during acute lung injury

2004 ◽  
Vol 286 (4) ◽  
pp. L834-L840 ◽  
Author(s):  
Delphine L. Chen ◽  
Daniel P. Schuster
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Pet Imaging ◽  
Fdg Pet ◽  
Pulmonary Sequestration ◽  
Fdg Uptake ◽  
Positron Emission ◽  
Activated Neutrophils ◽  
Neutrophil Kinetics

We measured neutrophil glucose uptake with positron emission tomographic imaging and [18F]fluorodeoxyglucose ([18F]FDG-PET) in anesthetized dogs after intravenous oleic acid-induced acute lung injury (ALI; OA group, n = 6) or after low-dose intravenous endotoxin (known to activate neutrophils without causing lung injury) followed by OA (Etx + OA group, n = 7). The following two other groups were studied as controls: one that received no intervention ( n = 5) and a group treated with Etx only ( n = 6). PET imaging was performed ∼1.5 h after initiating experimental interventions. The rate of [3H]deoxyglucose ([3H]DG) uptake was also measured in vitro in cells recovered from bronchoalveolar lavage (BAL) performed after PET imaging. Circulating neutrophil counts fell significantly in animals treated with Etx but not in the other two groups. The rate of [18F]FDG uptake, measured by the influx constant Ki, was significantly elevated ( P < 0.05) in both Etx-treated groups (7.9 ± 2.6 × 10-3ml blood·ml lung-1·min-1in the Etx group, 9.3 ± 4.8 × 10-3ml blood·ml lung-1·min-1in the Etx + OA group) but not in the group treated only with OA (3.4 ± 0.8 × 10-3ml blood·ml lung-1·min-1) when compared with the normal control (1.6 ± 0.4 × 10-3ml blood·ml lung-1·min-1). [3H]DG uptake was increased (73 ± 7%) in BAL neutrophils recovered from the Etx + OA group ( P < 0.05) but not in the OA group. Kiand [3H]DG uptake rates were linearly correlated ( R2= 0.65). We conclude that the rate of [18F]FDG uptake in the lungs during ALI reflects the state of neutrophil activation. [18F]FDG-PET imaging can detect pulmonary sequestration of activated neutrophils, despite the absence of alveolar neutrophilia. Thus [18F]FDG-PET imaging may be a useful tool to study neutrophil kinetics during ALI.

Detection of Inflammatory Lesions by F-18 Fluorodeoxyglucose Positron Emission Tomography in Patients with Polymyositis and Dermatomyositis

2012 ◽  
Vol 39 (8) ◽  
pp. 1659-1665 ◽  
Author(s):  
TAKAYOSHI OWADA ◽  
REIKA MAEZAWA ◽  
KAZUHIRO KURASAWA ◽  
HARUTSUGU OKADA ◽  
SATOKO ARAI ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Pet Imaging ◽  
Fdg Pet ◽  
Inflammatory Myopathy ◽  
Emission Tomography ◽  
Fluorodeoxyglucose Positron Emission Tomography ◽  
Muscle Diseases ◽  
Fdg Uptake ◽  
Positron Emission ◽  
Fluorodeoxyglucose Positron Emission

Objective.To evaluate the usefulness of F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging in the management of patients with inflammatory myopathy. We examined whether FDG-PET scanning detects myositis or extramuscular lesions in patients with polymyositis (PM) and dermatomyositis (DM).Methods.FDG-PET imaging was performed in 24 patients with active inflammatory myopathy (PM, 11; DM, 13). The images were read by radiologists in a blinded manner. FDG uptake into muscles was judged positive when the intensity of muscles was higher than or equal to that of the liver. As controls, FDG imaging findings of patients with a lung mass and without muscle diseases were used. To investigate associations between FDG-PET findings and clinical/laboratory findings, the patients’ medical records were reviewed retrospectively.Results.Increased FDG uptake in muscles was found in 8 of 24 (33%) patients. In 67 of 69 (97%) controls without muscle diseases, no muscle FDG uptake was detected. The sensitivity of FDG-PET to detect myositis was lower than that of electromyogram (EMG), magnetic resonance imaging, and muscle biopsy. There were no significant differences in clinical manifestations between patients with and without increased FDG uptake in muscles, although patients with FDG muscle uptake had a tendency to have extended myositis with endomysial cell infiltration. FDG-PET detected neoplasms in patients with associated malignancy. FDG uptake in lungs was found in 7 of 18 patients with interstitial lung disease.Conclusion.FDG-PET imaging has limited usefulness for the evaluation of myositis in patients with PM/DM because of its low sensitivity, although it might be useful for detection of malignancy in these patients.

Inhibition of CD18 or CD11b attenuates acute lung injury after acid instillation in rabbits

1997 ◽  
Vol 82 (6) ◽  
pp. 1743-1750 ◽  
Author(s):  
Hans G. Folkesson ◽  
Michael A. Matthay
Keyword(s):  
Monoclonal Antibody ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Normal Saline ◽  
Neutrophil Activation ◽  
Protein Accumulation ◽  
Lung Water ◽  
Activated Neutrophils ◽  
Factor Α

Folkesson, Hans G., and Michael A. Matthay. Inhibition of CD18 or CD11b attenuates acute lung injury after acid instillation in rabbits. J. Appl. Physiol. 82(6): 1743–1750, 1997.—Acid-induced lung injury is mediated primarily by activated neutrophils. Although a prior study demonstrated that acid-induced neutrophil influx into the air spaces was not CD18 dependent, we hypothesized that either a neutralizing anti-CD18 monoclonal antibody (MHM23) or a neutrophil inhibitory factor (NIF), NIF (CD11b,18), might attenuate acid-induced lung injury in rabbits by interfering with neutrophil activation. This hypothesis derived from in vitro studies that reported that anti-CD18 therapy prevented tumor necrosis factor-α-induced neutrophil activation. Hydrochloric acid (pH = 1.5 in one-third normal saline) or one-third normal saline (4 ml/kg) was instilled into the lungs of ventilated, anesthetized rabbits. The rabbits were studied for 6 h. In acid-instilled rabbits without the anti-CD18 monoclonal antibody or NIF (CD11b,18), severe lung injury developed. In acid-instilled rabbits, pretreatment (5 min before acid) with the anti-CD18 monoclonal antibody (2 mg/kg iv) or pretreatment with the NIF (anti-CD11b,18, 10 mg/kg iv) prevented 50–70% of acid-induced abnormalities in oxygenation, the increase in extravascular lung water, and extravascular protein accumulation. The anti-CD18 monoclonal antibody was associated with a significant increase in air space neutrophils by bronchoalveolar lavage, suggesting that the neutrophils respond normally to chemotactic stimuli but that the neutrophils did not injure the lung even though they accumulated in the air spaces. In summary, neutralization of CD18 attenuates the acute lung injury after acid instillation without reducing the number of neutrophils in the air spaces, suggesting that anti-CD18 therapy may be beneficial because of its capacity to reduce neutrophil activation.

The Two-Event Model of Transfusion-Related Acute Lung Injury: Antibodies to HNA-3a Cause PMN Cytotoxicity.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 832-832 ◽  
Author(s):  
Brian R. Curtis ◽  
Marguerite R. Kelher ◽  
Nathan J.D. McLaughlin ◽  
Patricia M. Kopko ◽  
Christopher C. Silliman
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Sequestration ◽  
Endothelial Damage ◽  
Healthy Donors ◽  
Group Control ◽  
Event Model ◽  
Stored Blood

Abstract Transfusion related acute lung injury (TRALI) is a serious complication of blood administration. TRALI is neutrophil (PMN)-mediated and the pathogenesis is due to the infusion of antibodies directed against specific HLA (class I or II) or granulocyte antigens and may also be the result of two events: 1) a predisposing clinical condition of the patient resulting in PMN pulmonary sequestration followed by 2) the infusion of biologic response modifiers (BRMs), e.g. lipids from stored blood. These BRMs prime PMNs in vitro and cause PMN cytotoxicity in vivo resulting in endothelial damage, capillary leak and TRALI. We hypothesize that antibodies directed against specific PMN antigens cause rapid PMN priming and cytotoxicity in a two-event model, specific to the antigen they recognize. PMNs were isolated from healthy donors and 5b− (HNA-3a−) donors by standard techniques and were incubated for 3 min with 10% fresh plasma (FP) from healthy donors, plasma from three donors who had antibodies against HNA-3a and were implicated in TRALI, or 10% immune complexes (ICs) made from sera (+ control). Selected wells had Fab′2 fragments against the Fc receptors (CD16, CD32 & CD64). The maximal rate of O2− production was measured as cytochrome c reduction at 550 nm. Priming is defined as augmentation of the fMLP-activated respiratory burst (Table 1). We used an in vitro model of TRALI (Wyman AJP Cell 283: C1592, 2002) in which Human plumonary microvascular endothelial cells (HMVECs) were grown to 90% confluence and incubated with buffer or endotoxin (LPS) [200 ng/ml] for 6 hours. HNA-3a+ PMNs were added ± Fab′2 fragments, allowed to settle, and incubated for 30 min with FP or HNA-3a+ plasma. The plates were forcibly decanted and the viable HMVECs per mm2 were counted (Table 2). HNA-3a+ plasma significantly primed the PMN oxidase as compared to FP-treated controls (Table 1). Pre-treatment of PMNs with Fab′2 inhibited IC priming but did not affect other groups, and HNA-3a+ plasma did not prime HNA-3a− PMNs (data not shown). HNA-3a+ plasma ± LPS without PMNs did not affect HMVEC viability (data not shown), and HMVECs activated with LPS caused widespread PMN adherence. HNA-3a+ plasma plus HNA-3a+ PMNs caused destruction of LPS-activated HMVECs that was partially inhibited by Fab′2 fragments (Table 2). We conclude that HNA-3a+ plasma rapidly, effectively, and specifically primes HNA3+ PMNs. HNA-3a+ plasma can also serve as the second event in a two-event model of PMN-mediated HMVEC damage. Thus, antibodies directed against specific granulocyte antigens and lipids from stored blood may cause TRALI through a common final pathway of PMN activation. HNA-3a+ (5b+) plasma priming of HNA-3a+ PMNs Pre-tx/Group Control ICs FFP Donor 1 Donor 2 Donor 3 Units=nmol O2−/min; †=P<0.05 versus FFP controls; *=p<0.05 versus ICs. Buffer 2.7±0.5 8.8±0.7† 2.5±0.4 5.7±1.8† 6.5±† 5.0±1.0† Fab′2 2.1±0.8 3.2±0.4* 3.6±0.9 3.8±0.7 4.6±1.5 4.0±1.0 HNA-3a+ (5b+) plasma causes PMN cytotoxicity Pre-tx/Group Control LPS/PMNs LPS/PMNs/FFP LPS/PMNs/5b plasma Units=viable HMVECs/mm2; †=p<0.05 versus Controls and LPS/PMNs/FFP; *=p<0.05 versus LPS/PMN/5b+ plasma. Buffer 245±1 234±8 229±9 151±7† Fab′2 no data no data 240±9 190±*

scholarly journals Development of a blood sample detector for multi-tracer positron emission tomography using gamma spectroscopy

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Carlos Velasco ◽  
Adriana Mota-Cobián ◽  
Jesús Mateo ◽  
Samuel España
Keyword(s):  
Positron Emission Tomography ◽  
Blood Sample ◽  
Pet Imaging ◽  
Spectroscopic Analysis ◽  
Gamma Spectroscopy ◽  
Emission Tomography ◽  
Blood Samples ◽  
Positron Emission

Abstract Background Multi-tracer positron emission tomography (PET) imaging can be accomplished by applying multi-tracer compartment modeling. Recently, a method has been proposed in which the arterial input functions (AIFs) of the multi-tracer PET scan are explicitly derived. For that purpose, a gamma spectroscopic analysis is performed on blood samples manually withdrawn from the patient when at least one of the co-injected tracers is based on a non-pure positron emitter. Alternatively, these blood samples required for the spectroscopic analysis may be obtained and analyzed on site by an automated detection device, thus minimizing analysis time and radiation exposure of the operating personnel. In this work, a new automated blood sample detector based on silicon photomultipliers (SiPMs) for single- and multi-tracer PET imaging is presented, characterized, and tested in vitro and in vivo. Results The detector presented in this work stores and analyzes on-the-fly single and coincidence detected events. A sensitivity of 22.6 cps/(kBq/mL) and 1.7 cps/(kBq/mL) was obtained for single and coincidence events respectively. An energy resolution of 35% full-width-half-maximum (FWHM) at 511 keV and a minimum detectable activity of 0.30 ± 0.08 kBq/mL in single mode were obtained. The in vivo AIFs obtained with the detector show an excellent Pearson’s correlation (r = 0.996, p < 0.0001) with the ones obtained from well counter analysis of discrete blood samples. Moreover, in vitro experiments demonstrate the capability of the detector to apply the gamma spectroscopic analysis on a mixture of 68Ga and 18F and separate the individual signal emitted from each one. Conclusions Characterization and in vivo evaluation under realistic experimental conditions showed that the detector proposed in this work offers excellent sensibility and stability. The device also showed to successfully separate individual signals emitted from a mixture of radioisotopes. Therefore, the blood sample detector presented in this study allows fully automatic AIFs measurements during single- and multi-tracer PET studies.

scholarly journals In vitro and in vivo assessment of the protective effect of sufentanil in acute lung injury

2021 ◽  
Vol 49 (2) ◽  
pp. 030006052098635
Author(s):  
Qi Gao ◽  
Ningqing Chang ◽  
Donglian Liu
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
High Mobility ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Inflammatory Factors ◽  
Luciferase Reporter ◽  
Hmgb1 Protein

Objectives To investigate the mechanisms underlying the protective effect of sufentanil against acute lung injury (ALI). Material and Methods Rats were administered lipopolysaccharide (LPS) by endotracheal instillation to establish a model of ALI. LPS was used to stimulate BEAS-2B cells. The targets and promoter activities of IκB were assessed using a luciferase reporter assay. Apoptosis of BEAS-2B cells was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling. Results Sufentanil treatment markedly reduced pathological changes in lung tissue, pulmonary edema and secretion of inflammatory factors associated with ALI in vivo and in vitro. In addition, sufentanil suppressed apoptosis induced by LPS and activated NF-κB both in vivo and in vitro. Furthermore, upregulation of high mobility group box protein 1 (HMGB1) protein levels and downregulation of miR-129-5p levels were observed in vivo and in vitro following sufentanil treatment. miR-129-5p targeted the 3ʹ untranslated region and its inhibition decreased promoter activities of IκB-α. miR-129-5p inhibition significantly weakened the protective effect of sufentanil on LPS-treated BEAS-2B cells. Conclusion Sufentanil regulated the miR-129-5p/HMGB1 axis to enhance IκB-α expression, suggesting that sufentanil represents a candidate drug for ALI protection and providing avenues for clinical treatment.

scholarly journals Group V Phospholipase A2 Mediates Endothelial Dysfunction and Acute Lung Injury Caused by Methicillin-Resistant Staphylococcus aureus

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1731
Author(s):  
Yu Maw Htwe ◽  
Huashan Wang ◽  
Patrick Belvitch ◽  
Lucille Meliton ◽  
Mounica Bandela ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Acute Lung Injury ◽  
Endothelial Dysfunction ◽  
Lung Injury ◽  
Phospholipase A2 ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Group V ◽  
Methicillin Resistant

Lung endothelial dysfunction is a key feature of acute lung injury (ALI) and clinical acute respiratory distress syndrome (ARDS). Previous studies have identified the lipid-generating enzyme, group V phospholipase A2 (gVPLA2), as a mediator of lung endothelial barrier disruption and inflammation. The current study aimed to determine the role of gVPLA2 in mediating lung endothelial responses to methicillin-resistant Staphylococcus aureus (MRSA, USA300 strain), a major cause of ALI/ARDS. In vitro studies assessed the effects of gVPLA2 inhibition on lung endothelial cell (EC) permeability after exposure to heat-killed (HK) MRSA. In vivo studies assessed the effects of intratracheal live or HK-MRSA on multiple indices of ALI in wild-type (WT) and gVPLA2-deficient (KO) mice. In vitro, HK-MRSA increased gVPLA2 expression and permeability in human lung EC. Inhibition of gVPLA2 with either the PLA2 inhibitor, LY311727, or with a specific monoclonal antibody, attenuated the barrier disruption caused by HK-MRSA. LY311727 also reduced HK-MRSA-induced permeability in mouse lung EC isolated from WT but not gVPLA2-KO mice. In vivo, live MRSA caused significantly less ALI in gVPLA2 KO mice compared to WT, findings confirmed by intravital microscopy assessment in HK-MRSA-treated mice. After targeted delivery of gVPLA2 plasmid to lung endothelium using ACE antibody-conjugated liposomes, MRSA-induced ALI was significantly increased in gVPLA2-KO mice, indicating that lung endothelial expression of gVPLA2 is critical in vivo. In summary, these results demonstrate an important role for gVPLA2 in mediating MRSA-induced lung EC permeability and ALI. Thus, gVPLA2 may represent a novel therapeutic target in ALI/ARDS caused by bacterial infection.

scholarly journals H2S in acute lung injury: a therapeutic dead end(?)

2020 ◽  
Vol 8 (S1) ◽  
Author(s):  
Tamara Merz ◽  
Nicole Denoix ◽  
Martin Wepler ◽  
Holger Gäßler ◽  
David A. C. Messerer ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Circulatory Shock ◽  
Therapeutic Window ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Clinical Reality ◽  
Dead End

AbstractThis review addresses the plausibility of hydrogen sulfide (H2S) therapy for acute lung injury (ALI) and circulatory shock, by contrasting the promising preclinical results to the present clinical reality. The review discusses how the narrow therapeutic window and width, and potentially toxic effects, the route, dosing, and timing of administration all have to be balanced out very carefully. The development of standardized methods to determine in vitro and in vivo H2S concentrations, and the pharmacokinetics and pharmacodynamics of H2S-releasing compounds is a necessity to facilitate the safety of H2S-based therapies. We suggest the potential of exploiting already clinically approved compounds, which are known or unknown H2S donors, as a surrogate strategy.

scholarly journals Long non-coding RNA OIP5-AS1 aggravates acute lung injury by promoting inflammation and cell apoptosis via regulating the miR-26a-5p/TLR4 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qingsong Sun ◽  
Man Luo ◽  
Zhiwei Gao ◽  
Xiang Han ◽  
Weiqin Wu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Cell Apoptosis ◽  
Quantitative Polymerase Chain Reaction ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Interacting Protein ◽  
Wide Range

Abstract Background Acute lung injury (ALI) is a pulmonary disorder that leads to acute respiration failure and thereby results in a high mortality worldwide. Increasing studies have indicated that toll-like receptor 4 (TLR4) is a promoter in ALI, and we aimed to explore the underlying upstream mechanism of TLR4 in ALI. Methods We used lipopolysaccharide (LPS) to induce an acute inflammatory response in vitro model and a murine mouse model. A wide range of experiments including reverse transcription quantitative polymerase chain reaction, western blot, enzyme linked immunosorbent assay, flow cytometry, hematoxylin–eosin staining, RNA immunoprecipitation, luciferase activity and caspase-3 activity detection assays were conducted to figure out the expression status, specific role and potential upstream mechanism of TLR4 in ALI. Result TLR4 expression was upregulated in ALI mice and LPS-treated primary bronchial/tracheal epithelial cells. Moreover, miR-26a-5p was confirmed to target TLR4 according to results of luciferase reporter assay. In addition, miR-26a-5p overexpression decreased the contents of proinflammatory factors and inhibited cell apoptosis, while upregulation of TLR4 reversed these effects of miR-26a-5p mimics, implying that miR-26a-5p alleviated ALI by regulating TLR4. Afterwards, OPA interacting protein 5 antisense RNA 1 (OIP5-AS1) was identified to bind with miR-26a-5p. Functionally, OIP5-AS1 upregulation promoted the inflammation and miR-26a-5p overexpression counteracted the influence of OIP5-AS1 upregulation on cell inflammatory response and apoptosis. Conclusion OIP5-AS1 promotes ALI by regulating the miR-26a-5p/TLR4 axis in ALI mice and LPS-treated cells, which indicates a promising insight into diagnostics and therapeutics in ALI.

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