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The role of the lectin pathway of the complement system in SARS-CoV-2 lung injury.

ABSTRACT: Although some evidence showed the activation of complement systems in COVID-19 patients, proinflammatory status and lectin pathway remain unclear. Thus, the present study aimed to demonstrate the role of MBL and ficolin-3 in the complement system activation and compared to pandemic Influenza A virus H1N1 subtype infection (H1N1pdm09) and control patients. A total of 27 lungs formalin-fixed paraffin-embedded samples (10 from H1N1 group, 6 from the COVID-19 group, and 11 from the control group) were analyzed by immunohistochemistry using anti-IL-6, TNF-alfa, CD163, MBL e FCN3 antibodies. Genotyping of target polymorphisms in the MBL2 gene was performed by real-time PCR. Proinflammatory cytokines such as IL-6 and TNF-alpha presented higher tissue expression in the COVID-19 group compared to H1N1 and control groups. The same results were observed for ICAM-1 tissue expression. Increased expression of the FCN3 was observed in the COVID-19 group and H1N1 group compared to the control group. The MBL tissue expression was higher in the COVID-19 group compared to H1N1 and control groups. The genotypes AA for rs180040 (G/A), GG for rs1800451 (G/A) and CC for rs5030737 (T/C) showed a higher prevalence in the COVID-19 group. The intense activation of the lectin pathway, with particular emphasis on the MBL pathway, together with endothelial dysfunction and a massive proinflammatory cytokines production, possibly lead to a worse outcome in patients infected with SARS-Cov-2. Moreover, 3 SNPs of our study presented genotypes that might be correlated with high MBL tissue expression in the COVID-19 pulmonary samples.

SUBMITTER: Malaquias MAS

PROVIDER: S-EPMC7677075 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesCutaneous ischemia/reperfusion (CI/R) injury has shown to play a significant role in chronic wounds such as decubitus ulcers, diabetic foot ulcers, atherosclerotic lesions, and venous stasis wounds. CI/R also plays a role in free tissue transfer in reconstructive microsurgery and has been linked to clinical burn-depth progression after thermal injury. While the role of the complement system has been elucidated in multiple organ systems, evidence is lacking with respect to its role in the skin. Therefore, we evaluated the role of the complement system in CI/R injury.MethodsUsing a single pedicle skin flap mouse model of acute CI/R, we performed CI/R in wild-type (WT) mice and complement knock out (KO) mice, deficient in either C1q (C1q KO; classical pathway inhibition), mannose-binding lectin (MBL null; lectin pathway inhibition) or factor B (H2Bf KO; alternative pathway inhibition). Following 10 h ischemia and 7 days reperfusion, mice were sacrificed, flaps harvested and flap viability assessed via Image J software. The flap necrotic area was expressed as % total flap area. In another group, mice were sacrificed following CI/R with 10 h ischemia and 48 h reperfusion. Two cranial skin flap samples were taken for gene expression analysis of IL1b, IL6, TNFα, ICAM1, VCAM1, IL10, IL13 using real-time polymerase chain reaction (RT-PCR).ResultsFollowing CI/R, MBL null mice had a statistically significant smaller %necrotic flap area compared to WT mice (10.6 vs. 43.1%; p<0.05) suggesting protection from CI/R. A significantly reduced mean %necrotic flap area was not seen in either C1q KO or H2Bf KO mice relative to WT (22.9 and 31.3 vs. 43.1%; p=0.08 and p=0.244, respectively). There were no statistically significant differences between groups for markers of inflammation (TNFα, ICAM1, VCAM1, IL1b, IL6). In contrast, mRNA levels of IL10, a regulator of inflammation, were significantly increased in the MBL null group (p=0.047).ConclusionsWe demonstrated for the first time a significant role of MBL and the lectin complement pathway in ischemia/reperfusion injury of the skin and a potential role for IL10 in attenuating CI/R injury, as IL10 levels were significantly increased in the tissue from the CI/R-protected MBL null group.

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The role of the lectin pathway of the complement system in SARS-CoV-2 lung injury.

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