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Pathogenesis exploration and timely intervention of lung injury is quite necessary as it has harmed human health worldwide for years. Ficolin B (Fcn B) is a recognition molecule that can recognize a variety of ligands and play an important role in mediating the cell cycle, immune response, and tissue homeostasis in the lung. However, the role of Fcn B in bleomycin (BLM)-induced lung injury is obscure. This study aims to investigate the sources of Fcn B and its mechanism in BLM-induced lung injury. WT, Fcna -/- , and Fcnb -/- mice were selected to construct the BLM-induced lung injury model. Lung epithelial cells were utilized to construct the BLM-induced cell model. Exosomes that were secreted from alveolar macrophages (AMs) were applied for intervention by transporting Fcn B. Clinical data suggested M-ficolin (homologous of Fcn B) was raised in plasma of interstitial lung disease (ILD) patients. In the mouse model, macrophage-derived Fcn B aggravated BLM-induced lung injury and fibrosis. Fcn B further promoted the development of autophagy and ferroptosis. Remarkably, cell experiment results revealed that Fcn B transported by BLM-induced AMs exosomes accelerated autophagy and ferroptosis in lung epithelial cells through the activation of the cGAS-STING pathway. In contrast, the application of 3-Methyladenine (3-MA) reversed the promotion effect of Fcn B from BLM-induced AMs exosomes on lung epithelial cell damage by inhibiting autophagy-dependent ferroptosis. Meanwhile, in the BLM-induced mice model, the intervention of Fcn B secreted from BLM-induced AMs exosomes facilitated lung injury and fibrosis via ferroptosis. In summary, this study demonstrated that Fcn B transported by exosomes from AMs exacerbated BLM-induced lung injury by promoting lung epithelial cells ferroptosis through the cGAS-STING signaling pathway.

Abstract Ficolins, encoded by FCN genes, are key pattern recognition molecules of the lectin complement pathway involved in immune complex clearance, a process often impaired in systemic lupus erythematosus (SLE). Genetic polymorphisms in FCN genes may influence disease susceptibility. However, their functional significance in SLE remains unclear. The present study aimed to investigate the association of selected FCN gene single-nucleotide polymorphisms (SNPs) with SLE, lupus nephritis (LN), and serum ficolin levels in a Western Indian cohort. Seven SNPs in FCN1 (rs2989727, rs1071583), FCN2 (rs7851696, rs17549193, rs7865453, rs17514136), and FCN3 (rs3813800) were genotyped in 200 SLE patients and 200 healthy controls using polymerase chain reaction (PCR) sequence-specific primer and PCR restriction fragment length polymorphism. Serum ficolin-1, -2, and -3 levels were measured using ELISA. Statistical analysis included χ2 test, Kruskal–Wallis test, and logistic regression to assess associations and calculate odds ratios with 95% confidence intervals. The analysis identified significant associations of FCN2 rs7851696, rs7865453, and rs17514136, as well as FCN3 rs3813800, with SLE susceptibility. Among LN patients, FCN1 rs2989727 and rs1071583, FCN2 rs17514136, and FCN3 rs3813800 showed significant associations. FCN3 rs3813800 was significantly associated with ficolin-3 levels, while FCN2 rs7865453 was associated with complement component 1q–circulation immune complex levels. These findings provide novel insight into associations of FCN gene polymorphisms with SLE and LN susceptibility, with genotype–phenotype correlations suggesting their biological relevance. Future longitudinal and mechanistic studies are warranted to validate these associations and explore their therapeutic potential.

Background Ficolins were originally identified as proteins that bind to transforming growth factor-β1 (TGF-β1). They are capable of activating the complement system through lectin pathway for immune system protection. Ficolin-2 and 3 have been identified in patients with interstitial lung diseases (ILD) and their function in these diseases is currently being explored. In contrast, the functional role of ficolin-1 in pulmonary fibrosis is still elusive and remains to be elucidated. Methods The expression of ficolin-1 in the plasma of idiopathic pulmonary fibrosis (IPF) and connective tissue disease (CTD)-ILD patients was first determined. As the orthologue of human ficolin-1, ficolin-B knockout and ficolin-B overexpression were used to establish bleomycin (BLM)-induced pulmonary fibrosis mouse model. Co-immunoprecipitation, immunofluorescence and RNA sequencing were utilized to explore and expound on the expression and the functional mechanism of ficolin-1 in pulmonary fibrosis. Results Compared with healthy controls, plasma ficolin-1 was significantly decreased in patients with IPF and CTD-ILD. In the bleomycin (BLM)-induced mice model, ficolin-B deficiency aggravated lung injury and fibrosis. There was also observed increase in TGF-β1 levels and enhanced downstream signaling. However, the overexpression of ficolin-B showed preventative and therapeutic efficacy against lung fibrosis. Furthermore, coimmunoprecipitation studies revealed the direct interaction between ficolin-1 and TGF-β1 in human plasma, which was further confirmed by the colocalization of ficolin-1 and TGF-β1 in lung tissues. Conclusions Ficolin-1 inhibits pulmonary fibrosis by directly binding to the key profibrogenic factor TGF-β1, marking it as a potential target for therapy in the treatment of fibrotic lung diseases.

The immune system starts to develop early in embryogenesis. However, at birth it is still immature and associated with high susceptibility to infection. Adaptation to extrauterine conditions requires a balance between colonization with normal flora and protection from pathogens. Infections, oxidative stress and invasive therapeutic procedures may lead to transient organ dysfunction or permanent damage and perhaps even death. Newborns are primarily protected by innate immune mechanisms. Collectins (mannose-binding lectin, collectin-10, collectin-11, collectin-12, surfactant protein A, surfactant protein D) and ficolins (ficolin-1, ficolin-2, ficolin-3) are oligomeric, collagen-related defence lectins, involved in innate immune response. In this review, we discuss the structure, specificity, genetics and role of collectins and ficolins in neonatal health and disease. Their clinical associations (protective or pathogenic influence) depend on a variety of variables, including genetic polymorphisms, gestational age, method of delivery, and maternal/environmental microflora.

The complement system is involved in promoting secondary injury after traumatic brain injury (TBI), but the roles of the classical and lectin pathways leading to complement activation need to be clarified. To this end, we aimed to determine the ability of the brain to activate the synthesis of classical and lectin pathway initiators in response to TBI and to examine their expression in primary microglial cell cultures. We have modeled TBI in mice by controlled cortical impact (CCI), a clinically relevant experimental model. Using Real-time quantitative polymerase chain reaction (RT-qPCR) we analyzed the expression of initiators of classical the complement component 1q, 1r and 1s (C1q, C1r, and C1s) and lectin (mannose binding lectin A, mannose binding lectin C, collectin 11, ficolin A, and ficolin B) complement pathways and other cellular markers in four brain areas (cortex, striatum, thalamus and hippocampus) of mice exposed to CCI from 24 h and up to 5 weeks. In all murine ipsilateral brain structures assessed, we detected long-lasting, time- and area-dependent significant increases in the mRNA levels of all classical (C1q, C1s, C1r) and some lectin (collectin 11, ficolin A, ficolin B) initiator molecules after TBI. In parallel, we observed significantly enhanced expression of cellular markers for neutrophils (Cd177), T cells (Cd8), astrocytes (glial fibrillary acidic protein—GFAP), microglia/macrophages (allograft inflammatory factor 1—IBA-1), and microglia (transmembrane protein 119—TMEM119); moreover, we detected astrocytes (GFAP) and microglia/macrophages (IBA-1) protein level strong upregulation in all analyzed brain areas. Further, the results obtained in primary microglial cell cultures suggested that these cells may be largely responsible for the biosynthesis of classical pathway initiators. However, microglia are unlikely to be responsible for the production of the lectin pathway initiators. Immunofluorescence analysis confirmed that at the site of brain injury, the C1q is localized in microglia/macrophages and neurons but not in astroglial cells. In sum, the brain strongly reacts to TBI by activating the local synthesis of classical and lectin complement pathway activators. Thus, the brain responds to TBI with a strong, widespread and persistent upregulation of complement components, the targeting of which may provide protection in TBI.

Activation of the inflammatory generating complement system might play a pathogenic role in spontaneous subarachnoid hemorrhage (SAH). We studied whether plasma and cerebrospinal fluid (CSF) levels of complement proteins were associated with angiographic vasospasm and cerebral ischemic lesions after SAH. Ficolin-1 (M-ficolin), ficolin-3 (H-ficolin), mannose-binding lectin (MBL), MBL-associated serine protease 2 (MASP-2), MASP-3, and MAp44 were analyzed in plasma of 45 SAH patients at 24 h after bleeding. Additionally, ficolin-1 levels were measured in cerebrospinal fluid (CSF) samples obtained 24 h after bleeding in 19 patients with external ventricular drainage placement. Angiographic vasospasm was identified using transcranial Doppler or angio-CT and considered symptomatic when new focal deficits or ischemic lesions appeared in follow-up neuroimaging. Functional outcome was assessed using modified Rankin scale (mRS) at 90 days. Higher plasma ficolin-1 levels (ng/ml) at 24 h were associated with poor Hunt and Hess (HH) grade at admission (mean 1158 (SD 360) vs 1654 (871), p  = 0.004) and were higher in patients developing angiographic vasospasm (1119.44 (374) vs 1514 (755), p  = 0.025) and cerebral ischemia (1067 (325) vs 1610 (766), p  = 0.003). In multivariate models adjusted for confounders, higher ficolin-1 remained associated with brain ischemic lesions (OR per 100 ng/ml 1.34, 95 %CI 1.04–1.73, p  = 0.026) and vasospasm (OR per 100 ng/ml of increase 1.26, 95 %CI 1.02–1.56, p  = 0.031). Patients with angiographic vasospasm and cerebral ischemic lesions had non-significantly lower ficolin-1 concentration in the CSF. Plasma ficolin-1 emerged as a marker of clinical severity and brain ischemia after SAH. Larger studies will be required to establish the therapeutic implications of this finding.

Lung diseases are among the leading causes of morbidity and mortality. Complement activation may prevent a variety of respiratory infections, but on the other hand, could exacerbate tissue damage or contribute to adverse side effects. In this review, the associations of factors specific for complement activation the lectin pathway (LP) with infections of the respiratory system, from birth to adulthood, are discussed. The most extensive data concern mannose-binding lectin (MBL) which together with other collectins (collectin-10, collectin-11) and the ficolins (ficolin-1, ficolin-2, ficolin-3) belong to pattern-recognition molecules (PRM) specific for the LP. Those PRM form complexes with MBL-associated serine proteases (MASP-1, MASP-2, MASP-3) and related non-enzymatic factors (MAp19, MAp44). Beside diseases affecting humanity for centuries like tuberculosis or neonatal pneumonia, some recently published data concerning COVID-19 are summarized.

The complement is the first line of immune defense system involved in elimination of invading pathogens and dying host cells. Its activation is mainly triggered by immune complexes or pattern recognition molecules (PRMs) upon recognition against non-self or altered self-cells, such as C1q, collectins, ficolins, and properdin. Recent findings have interestingly shown that the pentraxins (C-reactive protein, CRP; serum-amyloid P component, SAP; long pentraxin 3, PTX3) are involved in complement activation and amplification via communication with complement initiation PRMs, but also complement regulation via recruitment of complement regulators, for instance C4b binding protein (C4BP) and factor H (fH). This review addresses the potential roles of the pentraxins in the complement system during infection and inflammation, and emphasizes the underlining implications of the pentraxins in the context of complement activation and regulation both under physiological and pathological conditions.

ObjectiveDistinction on clinical grounds between acute lymphoblastic leukaemia presenting with arthropathy (ALLarthropathy) and juvenile idiopathic arthritis (JIA) is difficult, as the clinical and paraclinical signs of leukaemia may be vague. The primary aim was to examine the use of lectin complement pathway proteins as markers to differentiate ALLarthropathy from JIA. The secondary aims were to compare the protein levels at baseline and follow-up in a paired number of children with ALL and to examine the correlation with haematology counts, erythrocyte sedimentation reaction (ESR), C-reactive protein (CRP), blasts, relapse and death.Study designIn this observational study, we measured M-ficolin, CL-K1 and MASP-3 in serum from children with ALL (n=151) and JIA (n=238) by time-resolved immunofluorometric assays. Logistic regression was used for predictions of ALL risk, considering the markers as the respective exposures. We performed internal validation using repeated ‘10-fold cross-validation’ with 100 repetitions computing the area under the curve (AUC) as well as positive and negative predictive values in order to evaluate the predictive performance.ResultsThe level of M-ficolin was higher in JIA than ALLtotal and the ALLarthropathy subgroup. The M-ficolin level normalised after remission of ALL. M-ficolin could differentiate ALL from JIA with an AUC of 94% and positive predictive value (PPV) of 95%, exceeding CRP and haemoglobin. In a dichotomised predictive model with optimal cut-offs for M-ficolin, platelets and haemoglobin, AUC was 99% and PPV 98% in detecting ALL from JIA.ConclusionM-ficolin is a valuable marker to differentiate the child with ALL from JIA.

Pentraxin 3 (PTX3) and ficolin are the plasma phase of pattern recognition receptors (PRRs) and can activate complement through classical and lectin pathways, respectively, which may contribute to disease severity. This study aimed to investigate the association between PTX3 and ficolin with disease severity in patients with coronavirus disease-2019 (COVID-19). Seventy-three COVID-19 patients and 25 healthy controls were enrolled in this study. The participants were divided into three groups as follows: 14 patients as the intensive care unit (ICU) group, 59 patients as the non-ICU group, and 25 subjects as the healthy control group. The serum levels of PTX3 and ficolin were measured by enzyme-linked immunosorbent assay (ELISA) kits. Patients in ICU and non-ICU groups had significantly higher levels of PTX3 compared to the healthy control group ( p = 0.0002 and p = 0.0072, respectively). Patients in the ICU group also had an increased amount of PTX3 (1957 ± 1769 pg/ml) compared to non-ICU patients (1220 ± 1784 pg/ml). However, this difference was not significant. On the other hand, serum levels of ficolin were not different among the three groups. PTX3, as an acute phase protein, may contribute to disease severity. Its probable inflammatory role could result from the high activation of the complement system. On the other hand, it could be suggested that ficolin has no crucial role in the disease severity of COVID-19 patients.