Search Results (19)

Background: Surfactant Protein D (SP-D) is a critical immunomodulatory collectin maintaining alveolar homeostasis. Obstructive sleep apnea (OSA)-related intermittent hypoxia (IH) disrupts pulmonary surfactant integrity; however, severity-dependent SP-D dynamics remain incompletely characterized. This study explores SP-D as a potential indicator of IH-induced alveolar stress and evaluates whether Galectin-3 (Gal-3) inhibition modulates surfactant homeostasis. Methods: Forty adult male Sprague-Dawley rats (8 per group) were randomized to Control (normoxia), Moderate IH (MIH; 15–30 events/hour), Severe IH (SIH; 30–60 events/hour), MIH + Gal-3 inhibitor (Modified Citrus Pectin, 800 mg/kg/day), or SIH + Gal-3 inhibitor. IH exposure lasted 8 h/day for 10 days. Outcomes included circulating SP-D, Surfactant Protein B (SP-B), inflammatory markers, physiological parameters, and histopathological lung injury scores assessed via American Thoracic Society guidelines. Results: SP-D levels showed numerical reductions with increasing IH severity (Control: 1969.07 pg/mL [IQR: 262.15]; SIH: 1404.30 pg/mL [IQR: 351.88]), representing a 28.6% decrease. However, between-group variability resulted in non-significant omnibus testing (Kruskal–Wallis p = 0.187). Gal-3 inhibition elevated SP-D levels, particularly in severe IH (2133.95 pg/mL [IQR: 1240.70]), though high inter-individual variability was observed (CV = 58.1%). SP-B showed significant suppression under moderate IH (p = 0.019) with restoration by treatment. Exploratory correlation analysis revealed moderate positive associations between SP-D and heart rate (r = 0.587) and respiratory rate (r = 0.419) in severe IH, though these did not reach statistical significance (p = 0.126 and p = 0.301, respectively). Histologically, severe IH induced diffuse alveolar damage (total lung score: 19.67 ± 0.82). Gal-3 inhibition produced context-dependent effects: protective in severe IH but paradoxically exacerbating inflammation under moderate IH (29.20 ± 4.64 vs. 20.00 ± 4.34; p < 0.05). Gal-3 inhibition significantly attenuated cardiac injury (injury score: 0.00 ± 0.00 vs. 7.17 ± 0.75 in severe IH; p < 0.001, η² = 0.859). Conclusions: SP-D demonstrates severity-associated alterations consistent with alveolar epithelial stress during IH, though high variability limits definitive biomarker validation in this sample. Gal-3 inhibition modulates surfactant homeostasis and attenuates cardiopulmonary injury in a context-dependent manner. These findings support further investigation into SP-D as a component of multimodal severity stratification in OSA and highlight Gal-3 inhibition as a context-dependent anti-inflammatory strategy, pending validation in larger cohorts with tissue-level confirmation. Full article

Chronological age is an imprecise proxy for reproductive capacity, necessitating biomarkers that reflect the underlying pathophysiology of the ovary. Fibrotic remodeling of the ovarian stroma is a key hallmark of biological ovarian aging, yet it cannot be assessed by current clinical tools. This study aimed to identify and validate a novel serum biomarker for fibrotic ovarian aging by applying supervised machine learning (ML) to human ovarian transcriptomic data. Transcriptomic data from the Genotype-Tissue Expression (GTEx) database were analyzed using ML algorithms to identify candidate genes predictive of ovarian aging, and finally, fibroblast activation protein (FAP) and collectin-11 (COLEC11) were selected for clinical validation. In a cross-sectional study, serum levels of FAP and COLEC11, along with key hormonal indices, were measured in two nested patient cohorts, and their associations with ovarian reserve and clinical parameters were analyzed. Serum FAP levels did not correlate with age but showed a strong inverse correlation with anti-Müllerian hormone (AMH) (r = −0.61, p = 0.001), a finding accentuated in women with decreased ovarian reserve (DOR). While COLEC11 correlated with age, it failed to differentiate DOR status. FAP levels were independent of central hormonal regulation, consistent with preclinical fibrotic models. Circulating FAP reflects age-independent, fibrotic ovarian aging, offering stromal-specific information not captured by conventional hormonal markers. This study provides the first clinical validation of FAP as a biomarker for ovarian stromal aging, holding potential for improved reproductive risk assessment. Full article

Lectins from marine sponges have emerged as promising candidates for antimicrobial strategies, particularly against biofilm-forming pathogens. In this study, we report the purification, biochemical characterization, and antibiofilm properties of a new lectin (AfiL) isolated from Aplysina fistularis. AfiL exhibited typical features of sponge lectins, including a β-sheet-rich secondary structure and a predominant oligomeric state in solution. Dynamic light scattering (DLS) analyses confirmed that AfiL predominantly exists as a well-defined oligomer at acidic and neutral pH. Sequence analysis revealed similarity to a putative collectin-like protein from sponge Desydea avara. AfiL selectively agglutinated Staphylococcus aureus strains, correlating with its preferential binding to lipoteichoic acid (LTA). The lectin demonstrated significant antibiofilm activity against S. aureus, S. epidermidis, and Escherichia coli strains, and exhibited synergistic or additive effects when combined with conventional antibiotics against a Methicillin-resistant S. aureus. Isothermal titration calorimetry (ITC) revealed a strong interaction between AfiL and porcine stomach mucin (Kd = 1.71 × 10⁻⁶ M), consistent with multivalent carbohydrate recognition. Overall, our findings highlight the potential of AfiL as a novel antibiofilm agent with species-specific modulatory effects on antibiotic activity and provide new insights into the functional versatility of sponge-derived lectins in microbial control strategies. Full article

Surfactant proteins A and D (SP-A and SP-D) belong to the collectin subfamily of C-type oligomeric lectins. They are pattern-recognition molecules (PRMs), able to recognise pathogen- or danger-associated molecular patterns (PAMPs, DAMPs) in the presence of Ca²⁺ cations. That property enables opsonisation or agglutination of non-self or altered/abnormal self cells and contributes to their clearance. Like other collectins, SP-A and SP-D are characterised by the presence of four distinct domains: a cysteine-rich domain (at the N-terminus), a collagen-like region, an α-helical neck domain and a globular carbohydrate-recognition domain (CRD) (at the C-terminus). Pulmonary surfactant is a lipoprotein complex, preventing alveolar collapse by reducing surface tension at the air–liquid interface. SP-A and SP-D, produced by type II alveolar epithelial cells and Clara cells, are not only pattern-recognition molecules but also contribute to the surfactant structure and homeostasis. Moreover, they are expressed in a variety of extrapulmonary sites where they are involved in local immunity. The term “cancer” includes a variety of diseases: tumours start from uncontrolled growth of abnormal cells in any tissue which may further spread to other sites of the body. Many cancers are incurable, difficult to diagnose and often fatal. This short review summarises anti- and pro-tumorigenic associations of SP-A and SP-D as well as perspectives of their usefulness in cancer diagnosis and therapy. Full article

Valvular disease is a complex pathological condition that impacts countless individuals around the globe. Due to limited treatments, it is crucial to understand its mechanisms to identify new targets. Valve disease may result in pulmonary venous hypertension, which is linked to compromised functioning of the alveolar and capillary membranes and hindered gas exchange. Nonetheless, the correlation between surfactant proteins (SPs) and valve disease remains unexplored. A total of 44 patients were enrolled in this study, with 36 undergoing aortic valve replacement and 8 needing a second aortic valve substitution due to bioprosthetic valve degeneration. Ten healthy subjects were also included. The results showed that patients who underwent both the first valve replacement and the second surgery had significantly higher levels of immature SP-B (proSP-B) compared to control subjects. The levels of the extra-lung collectin SP-D were higher in patients who needed a second surgery due to bioprosthetic valve degeneration, while SP-A levels remained unchanged. The research also showed that there was no reciprocal relationship between inflammation and SP-D as the levels of inflammatory mediators did not differ between groups. The present study demonstrates that circulating proSP-B serves as a reliable marker of alveolar–capillary membrane damage in patients with valvular heart disease. Full article

Given the various clinical manifestations that characterize Coronavirus Disease 2019 (COVID-19), the scientific community is constantly searching for biomarkers with prognostic value. Surfactant proteins A (SP-A) and D (SP-D) are collectins that play a crucial role in ensuring proper alveolar function and an alteration of their serum levels was reported in several pulmonary diseases characterized by Acute Respiratory Distress Syndrome (ARDS) and pulmonary fibrosis. Considering that such clinical manifestations can also occur during Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, we wondered if these collectins could act as prognostic markers. In this regard, serum levels of SP-A and SP-D were measured by enzyme immunoassay in patients with SARS-CoV-2 infection (n = 51) at admission (T0) and after seven days (T1) and compared with healthy donors (n = 11). SP-D increased in COVID-19 patients compared to healthy controls during the early phases of infection, while a significant reduction was observed at T1. Stratifying SARS-CoV-2 patients according to disease severity, increased serum SP-D levels were observed in severe compared to mild patients. In light of these results, SP-D, but not SP-A, seems to be an eligible marker of COVID-19 pneumonia, and the early detection of SP-D serum levels could be crucial for preventive clinical management. Full article

Collectin-K1 (CL-K1) is a multifunctional C-type lectin that has been identified as playing a crucial role in innate immunity. It can bind to carbohydrates on pathogens, leading to direct neutralization, agglutination, and/or opsonization, thereby inhibiting pathogenic infection. In this study, we investigated a homolog of CL-K1 (OnCL-K1) in Nile tilapia (Oreochromis niloticus) and its role in promoting the clearance of the pathogen Streptococcus agalactiae (S. agalactiae) and enhancing the antibacterial ability of the fish. Our analysis of bacterial load displayed that OnCL-K1 substantially reduced the amount of S. agalactiae in tissues of the liver, spleen, anterior kidney, and brain in Nile tilapia. Furthermore, examination of tissue sections revealed that OnCL-K1 effectively alleviated tissue damage and inflammatory response in the liver, anterior kidney, spleen, and brain tissue of tilapia following S. agalactiae infection. Additionally, OnCL-K1 was found to decrease the expression of the pro-inflammatory factor IL-6 and migration inhibitor MIF, while increasing the expression of anti-inflammatory factor IL-10 and chemokine IL-8 in the spleen, anterior kidney, and brain tissues of tilapia. Moreover, statistical analysis of survival rates demonstrated that OnCL-K1 significantly improved the survival rate of tilapia after infection, with a survival rate of 90%. Collectively, our findings suggest that OnCL-K1 plays a vital role in the innate immune defense of resisting bacterial infection in Nile tilapia. It promotes the removal of bacterial pathogens from the host, inhibits pathogen proliferation in vivo, reduces damage to host tissues caused by pathogens, and improves the survival rate of the host. Full article

The complement system is the other major proteolytic cascade in the blood of vertebrates besides the coagulation–fibrinolytic system. Among the three main activation routes of complement, the lectin pathway (LP) has been discovered the latest, and it is still the subject of intense research. Mannose-binding lectin (MBL), other collectins, and ficolins are collectively termed as the pattern recognition molecules (PRMs) of the LP, and they are responsible for targeting LP activation to molecular patterns, e.g., on bacteria. MBL-associated serine proteases (MASPs) are the effectors, while MBL-associated proteins (MAps) have regulatory functions. Two serine protease components, MASP-1 and MASP-2, trigger the LP activation, while the third component, MASP-3, is involved in the function of the alternative pathway (AP) of complement. Besides their functions within the complement system, certain LP components have secondary (“moonlighting”) functions, e.g., in embryonic development. They also contribute to blood coagulation, and some might have tumor suppressing roles. Uncontrolled complement activation can contribute to the progression of many diseases (e.g., stroke, kidney diseases, thrombotic complications, and COVID-19). In most cases, the lectin pathway has also been implicated. In this review, we summarize the history of the lectin pathway, introduce their components, describe its activation and regulation, its roles within the complement cascade, its connections to blood coagulation, and its direct cellular effects. Special emphasis is placed on disease connections and the non-canonical functions of LP components. Full article

Retinal pigment epithelium (RPE) cell allotransplantation is seen as a possible solution to retinal diseases. However, the RPE-complement system triggered by the binding of collectin-11 (CL-11) is a potential barrier for RPE transplantation as the complement-mediated inflammatory response may promote T cell recognition. To address this, we investigated the role of CL-11 on T cell immuno-response. We confirmed that RPE cells up-regulated MHC class I and expressed MHC class II molecules in an inflammatory setting. Co-cultures of RPE cells with T cells led to the inhibition of T cell proliferation. We found that CL-11 was partially responsible for this effect as T cell binding of CL-11 inhibited T cell proliferation in association with the downregulation of CD28. We also found that the suppressive action of CL-11 was abrogated in the presence of the RGD peptide given to block the T cell binding of CL-11 by its collagen-like domain. Because RPE cells can bind and secrete CL-11 under stress conditions, we postulate that soluble CL-11 contributes to the immunosuppressive properties of RPE cells. The investigation of this dual biological activity of CL-11, namely as a trigger of the complement cascade and a modulator of T cell responses, may provide additional clues about the mechanisms that orchestrate the immunogenic properties of RPE cells. Full article

Establishing the rapid and accurate diagnosis of sepsis is a key component to the improvement of clinical outcomes. The ability of analytical platforms to rapidly detect pathogen-associated molecular patterns (PAMP) in blood could provide a powerful host-independent biomarker of sepsis. A novel concept was investigated based on the idea that a pre-bound and fluorescent ligand could be released from lectins in contact with high-affinity ligands (such as PAMPs). To create fluorescent ligands with precise avidity, the kinetically followed TEMPO oxidation of yeast mannan and carbodiimide coupling were used. The chemical modifications led to decreases in avidity between mannan and human collectins, such as the mannan-binding lectin (MBL) and human surfactant protein D (SP-D), but not in porcine SP-D. Despite this effect, these fluorescent derivatives were captured by human lectins using highly concentrated solutions. The resulting fluorescent beads were exposed to different solutions, and the results showed that displacements occur in contact with higher affinity ligands, proving that two-stage competition processes can occur in collectin carbohydrate recognition mechanisms. Moreover, the fluorescence loss depends on the discrepancy between the respective avidities of the recognized ligand and the fluorescent mannan. Chemically modulated fluorescent ligands associated with a diversity of collectins may lead to the creation of diagnostic tools suitable for multiplex array assays and the identification of high-avidity ligands. Full article

The complement system is an important branch of the humoral innate immune response that can be activated via three distinct pathways (classical, alternative, lectin), contributing to keeping/restoring homeostasis. It can also interact with cellular innate immunity and with components of acquired immunity. Cross-talk between the complement system and other enzyme-dependent cascades makes it a more influential defence system, but on the other hand, over- or chronic activation can be harmful. This short review is focused on the dual role of the lectin pathway of complement activation in human solid tumour cancers, including those of the female reproductive system, lung, and alimentary tract, with emphasis on the aforementioned cross-talk. Full article

Age-related macular degeneration (AMD) is a major cause of vision loss among the elderly in the Western world. The complement system has been identified as one of the main AMD disease pathways. We performed a comprehensive expression analysis of 32 complement proteins in plasma samples of 255 AMD patients and 221 control individuals using mass spectrometry-based semi-quantitative multiplex profiling. We detected significant associations of complement protein levels with age, sex and body-mass index (BMI), and potential associations of C-reactive protein, factor H related-2 (FHR-2) and collectin-11 with AMD. In addition, we confirmed previously described associations and identified new associations of AMD variants with complement levels. New associations include increased C4 levels for rs181705462 at the C2/CFB locus, decreased vitronectin (VTN) levels for rs11080055 at the TMEM97/VTN locus and decreased factor I levels for rs10033900 at the CFI locus. Finally, we detected significant associations between AMD-associated metabolites and complement proteins in plasma. The most significant complement-metabolite associations included increased high density lipoprotein (HDL) subparticle levels with decreased C3, factor H (FH) and VTN levels. The results of our study indicate that demographic factors, genetic variants and circulating metabolites are associated with complement protein components. We suggest that these factors should be considered to design personalized treatment approaches and to increase the success of clinical trials targeting the complement system. Full article

Histoplasmosis and pneumocystosis co-infections have been reported mainly in immunocompromised humans and in wild animals. The immunological response to each fungal infection has been described primarily using animal models; however, the host response to concomitant infection is unknown. The present work aimed to evaluate the pulmonary immunological response of patients with pneumonia caused either by Histoplasma capsulatum, Pneumocystis jirovecii, or their co-infection. We analyzed the pulmonary collectin and cytokine patterns of 131 bronchoalveolar lavage samples, which included HIV and non-HIV patients infected with H. capsulatum, P. jirovecii, or both fungi, as well as healthy volunteers and HIV patients without the studied fungal infections. Our results showed an increased production of the surfactant protein-A (SP-A) in non-HIV patients with H. capsulatum infection, contrasting with HIV patients (p < 0.05). Significant differences in median values of SP-A, IL-1β, TNF-α, IFN-γ, IL-18, IL-17A, IL-33, IL-13, and CXCL8 were found among all the groups studied, suggesting that these cytokines play a role in the local inflammatory processes of histoplasmosis and pneumocystosis. Interestingly, non-HIV patients with co-infection and pneumocystosis alone showed lower levels of SP-A, IL-1β, TNF-α, IFN-γ, IL-18, IL-17A, and IL-23 than histoplasmosis patients, suggesting an immunomodulatory ability of P. jirovecii over H. capsulatum response. Full article

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. Full article

The Malpuech, Michels, Mingarelli, Carnevale (3MC) syndrome is a rare, autosomal recessive genetic- disorder associated with mutations in the MASP1/3, COLEC1,1 or COLEC10 genes. The number of 3MC patients with known mutations in these three genes reported so far remains very small. To date, 16 mutations in MASP-1/3, 12 mutations in COLEC11 and three in COLEC10 associated with 3MC syndrome have been identified. Their products play an essential role as factors involved in the activation of complement via the lectin or alternative (MASP-3) pathways. Recent data indicate that mannose-binding lectin-associated serine protease-1 (MASP-1), MASP-3, collectin kidney-1 (collectin-11) (CL-K1), and collectin liver-1 (collectin-10) (CL-L1) also participate in the correct migration of neural crest cells (NCC) during embryogenesis. This is supported by relationships between MASP1/3, COLEC10, and COLEC11 gene mutations and the incidence of 3MC syndrome, associated with craniofacial abnormalities such as radioulnar synostosis high-arched eyebrows, cleft lip/palate, hearing loss, and ptosis. Full article