Research ArticleExperimental Studies
Open Access

Effect of Decay-accelerating Factor on LPS-induced Acute Lung Injury in the Rat

MARIA G. DETSIKA, IOANNA NIKITOPOULOU, STYLIANOS E. ORFANOS, IOANNA DIMOPOULOU and ANASTASIA KOTANIDOU
In Vivo November 2025, 39 (6) 3247-3257; DOI: https://doi.org/10.21873/invivo.14124

Abstract

Background/Aim: Complement activation has been implicated as a contributor to lung injury. Membrane-bound complement regulatory proteins, including decay-accelerating factor (DAF), control complement activation, thus mitigating complement-mediated injury. Their effect on lung injury remains unexplored. Using a DAF knockout rat model, we assessed the effect of DAF on the extent of lipopolysaccharide (LPS)-mediated acute lung injury (ALI) in rats.

Materials and Methods: Wild-type (WT) and DAF-knock out (Daf−/−) rats were injected intraperitoneally with a sublethal LPS dose. Following 16 h, protein and cytokine levels were assessed using immunohistochemistry/immunoblotting and ELISA, respectively.

Results: LPS administration to WT rats caused histopathological lesions indicative of ALI and significantly increased infiltrating inflammatory cells, as well as total number of cells and interleukin (IL)-6 levels, in bronchoalveolar lavage fluid samples. DAF absence resulted in increased C3b levels in Daf−/− control rats, compared with their WT controls. LPS administration to Daf−/− rats exacerbated lung injury without an effect on C3b levels. Higher baseline tissue protein levels of the anaphylatoxin complement component 5a receptor 1 (C5aR1) were observed in Daf−/− rats compared with WT whereas LPS administration to either group resulted in reduced levels of C5aR1, albeit not significant. DAF deficiency had no effect on baseline protein levels of CR1-related gene/protein Y (Crry) complement regulator, whereas LPS administration increased Crry protein levels to a similar extent in WT and Daf−/− rats.

Conclusion: DAF deficiency increased baseline C3b and C5aR1 protein levels in lung tissue. LPS-induced inflammatory response and lung injury were augmented in Daf−/− rats without further increase in C3b and in the absence of significant changes in the expression of membrane-bound complement regulatory proteins, DAF and Crry, or the anaphylatoxin receptor C5aR1.

Keywords:

Introduction

The complement system is an integral part of innate immunity mainly guarding against pathogens (1, 2). There are three pathways of complement activation, the classical, the alternative and the lectin pathway. Activation of the complement cascade involves sequential activation of the protein molecules, with activation of one molecule leading to cleavage and activation of the next (3).

Decay-accelerating factor (DAF) is a membrane-bound protein, belonging to a group of molecules known as complement activation regulatory proteins (CRegPs) (4, 5). CRegPs control the activation of the complement cascade and can be distinguished into the soluble CRegPs, which circulate freely in plasma and include C1 inhibitor, C4b binding protein, Factor H, and vitronectin, and membrane bound CregPs, which in humans, include DAF (CD55), CD46 and CD59 (6).

DAF is a 70 kDa glycoprotein attached to the cell membrane via a glycosylphosphatylinositol (GPI)-anchored domain (7). It binds the complement components C3b and C4b thus preventing assembly and accelerating decay of C3 convertase and C5 convertase (8) and regulating activation of all pathways (9, 10). These convertases cleave C3 and C5 into the soluble C3a and C5a fragments and the membrane-bound C3b and C5b (11). C3a and C5a, also known as anaphylatoxins, have potent pro-inflammatory and chemotactic properties (12, 13). Membrane-bound C3b further induces formation of the C5a convertase and acts as an opsonin (14) whereas C5b facilitates assembly of the lytic, membrane attack complex (MAC, C5b-9) (15). Therefore, it contributes to the elimination of generation and deposition of C3b on the cell membrane and the attenuation of MAC assembly.

In mice, there are two isoforms of DAF, a GPI-anchored and a transmembrane form, derived from two different genes (Daf1 and Daf2) (16). In rats, there are three different DAF isoforms; GPI-DAF, a transmembrane DAF form, and a secreted form (17). Rat DAF expression has been verified in most tissues and organs with the strongest expression in rat endothelial tissue and weak expression in brain tissue and circulating and spleen-resident T cells (17).

CregPs research in rodents further identified CR1-related gene/protein Y, (Crry), protein as the CD46 analogue in mice and rats (18-20). Although Crry is also membrane bound, its’ structure differs from that of DAF, as it is attached on the membrane via a transmembrane domain (21). However, functionally, it has been reported to combine the properties of human DAF and MCP thus affecting complement activation at both the C3 and C5 steps (20).

Few reports have assessed a possible role of CRegPs in mediating acute lung injury (ALI). Most studies have reported findings primarily in mice but the variation of CRegPs expression in different rodents raises questions over their functional role across species while a recent study identified a role for DAF in alleviating inflammation by inhibition of the C3 convertase (22). To address this question, our study investigated the potential role of the membrane-bound CRegP, DAF, using transgenic, Daf knock-out (Daf−/−), rats in which lipopolysaccharide (LPS)-mediated hyperinflammation associated with ALI was induced. In this established model, we also assessed changes in expression of the membrane-bound CRegP, Crry and the G-protein-coupled receptor, complement component 5a receptor 1, (C5aR1), which is a strong mediator of chemotaxis and pro-inflammatory cellular transformation.

Materials and Methods

Reagents. Antibodies for detection of rat DAF (clone RDIII-7 cat no: HM3035), rat C3/C3b (clone 2B10B9B2, cat no: HM3031), rat Crry (clone TLD-1C11, cat no: HM3032) and rat C5aR (clone mAb R63, cat no: HM3017) were purchased from Hycult (Uden, the Netherlands). GAPDH antibody (clone 14C10, cat no: 2118) was purchased from Cell Signaling Technology (Danvers, MA, USA).

Animals. Male Sprague-Dawley rats, 180 g in body weight, were used in this study. Animals were reared in accordance with the European Union Directive for the care and use of laboratory animals. All methods were carried out in accordance with relevant guidelines and regulations and are reported in accordance with ARRIVE guidelines. All procedures were approved by the Hellenic Veterinary Administration (Athens, Greece) (Protocol Approval no: 376023, date: 13/05/2021). Animals were housed at 20-22°C, with 55±5% humidity, a 12-hour light-dark cycle and daily monitored. Food and water were provided ad-libitum during the experiment period.

Animal study and samples. WT and Daf−/− rats were injected intraperitoneally with 8 mg/kg of LPS prepared from Escherichia coli O111:B4 (Sigma-Aldrich, Steinheim, Germany) under isoflurane anesthesia. Control mice received sterile saline solution. Four rats were included in each group. Rats were euthanized under anaesthesia at 16 h post injection and blood samples were obtained from the abdominal inferior vena cava. After centrifugation at 2,000 ×g for 10 min at 4°C, serum was collected and stored at −80°C. Bronchoalveolar lavage fluid (BALF) was obtained via tracheotomy by injecting and slowly withdrawing 0.5 ml of phosphate-buffered saline (PBS) and repeating this procedure three times. The fluid was separated from cellular components by centrifugation at 405 ×g for 10 min at 4°C, and supernatants were stored at −80°C. Total cell counting in BALF was performed manually using an improved Neubauer haemocytometer according to common procedures. Lungs from sacrificed rats were immersed in 4% neutral buffered paraformaldehyde for 24 h before embedding in paraffin. All invasive experimental procedures were carried out under ketamine:xylazine (1:3, 0.1 ml/100 g body weight) anesthesia.

Hematoxylin/eosin staining. Five μm sections of paraffin-embedded lungs were stained with hematoxylin and eosin according to standard histological procedures. Microscopic lung structure was observed under an Olympus (BX50F4) microscope (Hachioji, Tokyo, Japan).

Histological acute lung injury score. Paraffin-embedded lungs were graded for the presence and degree of lung injury using light microscopy. A lung injury score was determined, according to the official American Thoracic Society (ATS) report for measurement of experimental acute lung injury in animals. The following features were scored: focal thickening of alveolar membranes, congestion (distended blood vessels), interstitial and intra-alveolar neutrophil infiltration. Each characteristic was given a score from 0 to 3 (where 0: absence, 1: mild, 2: moderate and 3: severe) by a pathologist in a blinded manner and six different fields from each lung section examined were included as previously described (23).

BALF total protein. Total protein concentration in BALF samples of experimental animals was used as a marker of permeability of alveo-capillary membranes as previously described (24). Total protein concentration in BALF was determined using the Bio-Rad Dc Protein Assay kit (Bio-Rad Laboratories, Hercules, CA, USA) according to the manufacturer’s instructions.

Immunohistochemistry. Five μm sections of paraffin-embedded tissues were heat-treated in citric acid buffer and then incubated with 2% H2O2 to inactivate endogenous peroxidase. After blocking with 3% FBS, sections were incubated with primary antibodies (1:50 dilution) in a humidified chamber overnight at 40C. The primary antibodies used were anti-Crry, anti-C3/C3b and anti-DAF. Antibody binding was detected using Vectastain ABC Kit (Vector Laboratories, Burlingame, CA, USA) according to manufacturer’s instructions. Visualization using 3,3-diaminobenzidine as chromogen was performed using a DAB peroxidase substrate kit (Vector Laboratories). Slides were counterstained with hematoxylin, dehydrated, mounted with DPX medium (Sigma-Aldrich, St. Louis, MO, USA) and observed under an Olympus (BX50F4) microscope (Olympus). Quantification of immunohistochemistry was performed as previously described (25). Briefly, four randomly chosen areas of the tissue section of each animal of the same group, were photographed and staining was quantified using ImageJ software (National Institutes of Health, Bethesda, MD, USA; Laboratory for Optical and Computational Instrumentation, University of Wisconsin at Madison, Madison, WI, USA).

IL-6 and IL-10 ELISA immunoassays. Concentrations of IL-6 and IL-10 in rat BALF samples were determined using commercially available Elisa kits purchased from R & D systems (cat no: R6000B and cat no: R100; Minneapolis, MN, USA). All procedures were performed according to manufacturer’s instructions.

Western blot analysis. Protein lysates were resolved using SDS-PAGE, transferred onto polyvinyledinedifluoride membrane, and probed with primary antibodies for C3b (1:100 dilution in 5% milk/PBS/0.1% Tween), C5aR1 (1:50 dilution in 5% milk/PBS/0.1% Tween), Crry (1:500 dilution in 5% milk/PBS/0.1% Tween) and DAF (1:1,000 dilution in 5% milk/PBS/0.1% Tween), overnight at 4°C. Following, three 10 min washes with PBST, two-hour incubations with secondary antibodies (anti-mouse 1:2,000 dilution in 5% milk/PBS/0.1% Tween) were performed at room temperature. Membranes were washed with PBST and visualized in an iBright Imager (Invitrogen, Waltham, MA, USA) following incubation with ECL reagent, from Santa Cruz Biotechnology (Dallas, TX, USA). Equal loading was determined by probing for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (Cell Signaling Technology).

Statistical analysis. Data are presented as means±SEM. Statistical analysis was performed using the GraphPad Prism 8.0 software for Windows (GraphPad Software, Inc. Boston, MA, USA). Comparisons were made using One-way ANOVA testing in case of data normality or using the non-parametric Kruskal-Wallis test when normality was not obtained and the Fisher’s least significance test for post-hoc analysis. p<0.05 was considered statistically significant.

Results

LPS induced ALI in the absence of DAF. Administration of a sublethal dose of LPS (8 mg/kg) resulted in disrupted lung tissue architecture that was augmented in Daf−/− rats (Figure 1A). Lesions included interalveolar edema formation, thickening of the alveolar space and interstitial inflammatory cell infiltration with presence of inflammatory cells within alveolar air spaces. Assessment of changes in the lung injury score determined by the presence of focal thickening of alveolar membranes, congestion (distended blood vessels), interstitial and intra-alveolar neutrophil infiltration demonstrated a significant increase of total ALI score levels in both WT and Daf−/− rats receiving LPS. The increase of ALI score was significantly greater in the LPS administered Daf−/− rats compared to the respective WT group (Figure 1B). These lesions indicative of endotoxemia following LPS administration were also accompanied by increased total cell count in BALF and increased membrane permeability as assessed by total protein levels (Figure 1C and D). LPS-treatment significantly increased BALF cell counts and total protein levels in both WT and Daf−/− rats following LPS administration. The increase in BALF cell counts in Daf−/− rats was significantly higher compared to that in WT (Figure 1C) but the same was not observed for membrane permeability (Figure 1D).

Figure 1.
Figure 1.

Effect of lipopolysaccharide (LPS) administration on histopathology of wild type (WT) and Daf knock-out (Daf−/−) rats. A) Hematoxylin-eosin staining of lung tissue sections of WT and Daf−/− rats following saline (control) or LPS administration (16 h) Magnification at ×200. B) Total acute lung injury score levels assessed in histological lung tissue sections from all groups of animals. C) Total cell counts in BALF samples obtained from WT and Daf−/− rats following saline (control) or LPS administration. D) Total protein levels in BALF samples of WT and Daf−/− rats following saline (control) or LPS administration. Bars represent mean±SEM (n=4). Statistical analysis performed using One-way Anova testing for more than two group comparisons or Kruskal-Wallis testing when data normality was not obtained. Post-hoc analysis performed using Fisher’s least significant difference test. *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001.

Cytokine induction in response to LPS. We next investigated the changes in IL-6 and IL-10 cytokine levels in both BALF and serum samples (Figure 2). Concentrations of both cytokines were significantly increased in BALF samples of both WT and Daf−/− rats 16 h post LPS administration compared to controls (Figure 2), whereas IL-6 levels in LPS treated Daf−/− rats were significantly elevated compared with WT controls. In contrast, the levels of IL-10 remained similar between WT and Daf−/− rats treated with LPS (Figure 2).

Figure 2.
Figure 2.

Cytokine profile of wild type (WT) and Daf knock-out (Daf−/−) rats following lipopolysaccharide (LPS) administration. IL-6 and IL-10 levels in BALF samples obtained from WT and Daf−/− rats following saline (control) or LPS administration (16 h). Bars represent mean±SD. Statistical analysis performed using One-way Anova testing for more than two group comparisons. Post-hoc analysis performed using Fisher’s least significant difference test. *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001.

Complement deposition in response to LPS. We next investigated complement deposition in lung tissues of WT and Daf−/− rats in response to LPS. Lung tissue samples were stained for C3b, DAF, Crry. Staining for C3b was not detected in WT rats receiving either saline or LPS whereas weak C3b staining was observed in both groups of Daf−/− rats independent of LPS administration (Figure 3A). DAF deficiency had no effect on baseline protein levels of the membrane-bound complement regulator, Crry (Figure 3C). Crry levels increased to a similar extent in both WT and Daf−/− rats following LPS administration (Figure 3C) indicating an induction of Crry expression in response to LPS in lung tissue, independent of DAF presence (Figure 3C). C5aR1 staining was located mainly in bronchial epithelial cells (Figure 3D). No significant changes were detected in C5aR1 or DAF staining in either WT or Daf−/− control or LPS receiving rats (Figure 3B and D).

Figure 3.
Figure 3.

Complement regulation in wild type (WT) and Daf knock-out (Daf−/−) rats following lipopolysaccharide LPS administration. Lung tissue sections were obtained from WT and Daf−/− rats following LPS administration (16 h) and stained for A) C3b deposition and B) DAF C) Crry and D) C5aR1 expression. Magnification at 400×. Quantification of staining is shown for each protein. Bars represent mean±SEM. Statistical analysis performed using One-way Anova testing for more than two group comparisons or Kruskal-Wallis testing when data normality was not obtained. Post-hoc analysis performed using Fisher’s least significant difference test. **p<0.01.

Changes in C3b, DAF, Crry and C5aR1 protein levels were assessed using western blotting of lung tissue protein lysates. In Daf−/− rats, C3b protein levels increased, and DAF protein was undetectable and remained so in response to LPS treatment (Figure 4A). LPS administration exacerbated lung injury (Figure 1A and B) without an effect on C3b levels (Figure 4A). Western blotting for detection of C5a receptor levels was performed using an antibody specific for detection of CD88 (C5aR1). Baseline tissue protein levels of C5aR1 in Daf−/− rats were higher compared to those in WT controls, but this difference was not significant (Figure 4B). LPS administration did not result in significant changes of C5aR1 levels in either group. However, a decrease in C5aR1 levels was observed in both WT and Daf−/− rats in response to LPS.

Figure 4.
Figure 4.

Lung tissue complement regulation in wild type (WT) and Daf knock-out (Daf−/−) rats following lipopolysaccharide (LPS) administration using western blotting. Protein lysates derived from lung tissue samples were obtained from WT and Daf−/− rats following LPS administration (16 h) and analyzed using SDS-page for A) C3b deposition and B) DAF and C5aR1 expression (C). Graphs represent densitometric analysis results for C3b and C5aR over GAPDH used as loading control. Bars represent mean±SEM. Statistical analysis performed using One-way Anova testing for more than two group comparisons. Post-hoc analysis performed using Fisher’s least significant difference test. *p<0.05.

Discussion

The role of complement in ALI has been widely investigated and numerous reports have identified key ALI mediators belonging in the complement cascade (26). In this respect the C5a/C5aR axis is considered an important contributor to ALI as shown by studies which determined the reduction of ALI by efficient blocking of C5a and C5aR (27) or using transgenic models such as C5aR depleted mice (28). Furthermore, it was recently identified that the lectin pathway of the complement cascade is also a major contributor to ALI (29). Administration of an MASP-2 inhibitor, in order to block this important lectin pathway enzyme, in an LPS model of ALI in mice, ameliorated ALI and completely inhibited lectin pathway activation (29). Although the activation of complement is considered as a major contributor to ALI little is known about the role of CRegPs, such as DAF, in ALI establishment. This was addressed in the present study.

We previously characterized a novel Daf−/− transgenic rat model generated using a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/ associated protein 9 (Cas9) genome editing method, with complete DAF absence in all tissues examined including the lung (30). Using this transgenic rat model of DAF deficiency, we investigated the effect of complement regulation on LPS-mediated lung injury. DAF absence resulted in increased lung injury in rats receiving LPS, verified by the presence of histological damage and increased number of cells in BALF samples, indicative of LPS mediated lung injury (Figure 1) pointing to DAF as an important mediator of ALI. Furthermore, LPS receiving Daf−/− rats, exhibited significantly elevated IL-6 levels in comparison to WT respective controls (Figure 2) further supporting the role of DAF as a mediator of the inflammatory response in the lung. This is in accordance with a previous study, which also reported augmented levels of cytokines IL-6, IL-1β and TNF-a in Daf−/− mice following LPS administration (31). The study utilized Daf−/− mice in order to unravel the relationship between complement activation and Toll-like receptor (TLR) in the LPS-mediated inflammatory response and demonstrated exacerbation of the inflammatory response in Daf−/− mice. In the present study, we also assessed IL-10 levels, which were found at similar levels to WT controls in contrast to previous observations in mice (31) showing elevated levels of IL-10 in Daf−/− mice in comparison to control. However, sampling was performed at a much earlier time point (three hours), compared with our study, in which, rats were treated with LPS for 16 h. In our study, we utilized a 16 h time point for the LPS administration group of animals. This was based on prior observations in a similar model of LPS lung injury in mice (32). In a previous study by our group, assessing the effects of endotoxin on pro- and anti-inflammatory cytokines in mice, various time points (2, 4, 6, and 16 h) after endotoxin injection were included. Data showed that both circulating and BALF IL-6 and IL-10 cytokine levels were increased in LPS-challenged mice at the 16-h time point post injection.

Western blotting of extracts of lung tissue sections from Daf−/− control rats, receiving saline, showed augmented C3b deposition (Figure 4A) indicating that absence of DAF affects spontaneous C3b deposition in lung tissue. LPS administration did not result in significant changes of C3b lung deposition in either WT or Daf−/− rats suggesting that LPS-mediated lung injury is independent from C3b deposition. A slight reduction of C3b levels was observed in WT rats receiving LPS. Interestingly, LPS administration also resulted in stronger staining for Crry in both WT and Daf−/− rats indicating a possible induction of Crry expression in response to LPS, which could account for the reduction of C3b deposition in the lung of WT LPS receiving rats. The increased C3b deposition observed in the lung of Daf−/− rats raises questions about the effect of C3 in the LPS-mediated ALI model of the present study. A recent study reported a protective effect of C3 in a mouse model of bacterial-mediated pneumonia (33). The study demonstrated that C3−/− mice suffered from severe pneumonia and this was attributed to the production of C3 locally by lung epithelial cells.

Previous studies have investigated, the role of C5a-C5aR (C5aR1 and C5L2 receptors) axis in mediating LPS-induced ARDS (28, 34-36). However, the direct effect of DAF on C5aR1 expression in the lung has not been assessed previously. Although, non-significant, our data indicate an increase of lung tissue C5aR1 expression in the absence of DAF (Figure 4B). This was also supported by the immunohistochemistry results for C5aR1 expression, which revealed an increase in C5aR1 levels in Daf−/− rats compared to WT although it did not reach statistical significance (Figure 3D). Furthermore, LPS administration resulted in a trend of reduced C5aR1 expression levels in the lung tissue, albeit non-significant, at the specific time point. Previous studies in mice have identified a role for C5aR1 and C5aR2 in LPS-mediated ALI (28, 35). Specifically, using either antagonists or inhibitors of C5aR1 as well as gene disruption of C5aR1 or C5L2 a direct effect of both receptors on LPS-mediated injury by significantly attenuating severity of lung tissue disruption and injury as well as elevated cytokine levels in BALF samples has been revealed (35). Another study, which utilized a C5aR inhibitor in an LPS-induced ALI model in rats also demonstrated that inhibition of C5aR ameliorated lung injury (37). The decrease of C5aR1 expression observed in our study in response to LPS may possibly account for the exacerbation of lung injury detected by histology and increased BALF sample cell counts observed in both WT and Daf−/− rats. Furthermore, although Daf−/− rats had increased C5aR1 expression this was not sufficient to protect rats following LPS administration.

The role of pyroptosis in the effect of the C5-C5aR1 axis on ALI has also been assessed (37). The study employed a similar LPS endotoxin model of injury in rats and reported increased levels of C5aR1 in lung protein lysates following LPS administration in contrast to our findings. However, the study employed much greater concentrations of LPS (50 mg/kg) and its administration was performed by intratracheal instillation, which could possibly explain this discrepancy. The study also identified pyroptosis as a potential mediator of C5-C5aR1-dependent ALI. Specifically, using a C5aR inhibitor they showed that ALI was alleviated and pyroptosis was reduced. It is not known whether pyroptosis could also be playing a role in the Daf−/− rat model of ALI employed in our study as we did not assess changes in pyroptosis but it is a mechanism that could be explored.

Another known mediator of LPS-induced ALI is TLR4 and its interaction with DAF has been previously assessed in mice (31). In our study we did not assess this interaction, which could also be contributing to the increased injury observed in Daf−/− rats receiving LPS.

Taken together, our data point to a protective role of DAF against ALI in rats in line with similar reports in mice. However, one limitation of our study is the lack of measurements of C3a and C5a concentrations in plasma samples of Daf−/− rats as well as in WT rats following LPS administration, which would have assisted in determining the effect of C3a or C5a fragments. As DAF accelerates the decay of both C3a and C5a convertases and therefore acts at both steps of the cascade, analysis of C3a and C5a levels would have provided valuable evidence for addressing which step plays a key role in the specific LPS rat model utilized. However, our observations provide novel observations regarding the effect of DAF on LPS-mediated ALI and possibly point towards a synergistic effect between the C3 and C5 steps.

Another limitation is the relatively small number of animals included per group (n=4). Nonetheless, the ALI model is a well-established lung injury model with relatively modest variability when performed appropriately.

In summary, our study identified DAF as a mediator of LPS-induced ALI. The effect of DAF on ALI in rats appears independent of C3b or C5aR1. The findings of the current study support the important role of complement activation in ALI and emphasize the need to unravel underlying mechanistic pathways.

Footnotes

  • Authors’ Contributions

    MGD and IN performed the experimental work, acquired and interpreted the data and wrote the main manuscript. MGD and AK conceived the idea and the project framework. SEO, ID and AK supervised the project, reviewed and approved the manuscript. All Authors approved the manuscript.

  • Conflicts of Interest

    The Authors declare no competing interests in relation to this study.

  • Artificial Intelligence (AI) Disclosure

    No artificial intelligence (AI) tools, including large language models or machine learning software, were used in the preparation, analysis, or presentation of this manuscript.

  • Received July 1, 2025.
  • Revision received July 15, 2025.
  • Accepted July 22, 2025.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).

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Effect of Decay-accelerating Factor on LPS-induced Acute Lung Injury in the Rat
MARIA G. DETSIKA, IOANNA NIKITOPOULOU, STYLIANOS E. ORFANOS, IOANNA DIMOPOULOU, ANASTASIA KOTANIDOU
In Vivo Nov 2025, 39 (6) 3247-3257; DOI: 10.21873/invivo.14124
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