Maternal Larp6 controls oocyte development, chorion formation and elevation.

La-related protein 6 (Larp6) is a conserved RNA-binding protein found across eukaryotes that has been suggested to regulate collagen biogenesis, muscle development, ciliogenesis, and various aspects of cell proliferation and migration. Zebrafish have two Larp6 family genes: larp6a and larp6b Viable and fertile single and double homozygous larp6a and larp6b zygotic mutants revealed no defects in muscle structure, and were indistinguishable from heterozygous or wild-type siblings. However, larp6a mutant females produced eggs with chorions that failed to elevate fully and were fragile. Eggs from larp6b single mutant females showed minor chorion defects, but chorions from eggs laid by larp6a;larp6b double mutant females were more defective than those from larp6a single mutants. Electron microscopy revealed defective chorionogenesis during oocyte development. Despite this, maternal zygotic single and double mutants were viable and fertile. Mass spectrometry analysis provided a description of chorion protein composition and revealed significant reductions in a subset of zona pellucida and lectin-type proteins between wild-type and mutant chorions that paralleled the severity of the phenotype. We conclude that Larp6 proteins are required for normal oocyte development, chorion formation and egg activation.

Paracoccin Overexpression in Paracoccidioides brasiliensis Enhances Fungal Virulence by Remodeling Chitin Properties of the Cell Wall.

BACKGROUND: The thermodimorphic fungi Paracoccidioides spp. are the etiological agents of paracoccidioidomycosis. Although poorly studied, paracoccin (PCN) from Paracoccidioides brasiliensis has been shown to harbor lectinic, enzymatic, and immunomodulatory properties that affect disease development. METHODS: Mutants of P. brasiliensis overexpressing PCN (ov-PCN) were constructed by Agrobacterium tumefaciens-mediated transformation. ov-PCN strains were analyzed and inoculated intranasally or intravenously to mice. Fungal burden, lung pathology, and survival were monitored to evaluate virulence. Electron microscopy was used to evaluate the size of chito-oligomer particles released by ov-PCN or wild-type strains to growth media. RESULTS: ov-PCN strains revealed no differences in cell growth and viability, although PCN overexpression favored cell separation, chitin processing that results in the release of smaller chito-oligomer particles, and enhanced virulence. Our data show that PCN triggers a critical effect in the cell wall biogenesis through the chitinase activity resulting from overexpression of PCN. As such, PCN overexpression aggravates the disease caused by P. brasiliensis. CONCLUSIONS: Our data are consistent with a model in which PCN modulates the cell wall architecture via its chitinase activity. These findings highlight the potential for exploiting PCN function in future therapeutic approaches.

Lectin-Mediated Bacterial Modulation by the Intestinal Nematode Ascaris suum.

Ascariasis is a global health problem for humans and animals. Adult Ascaris nematodes are long-lived in the host intestine where they interact with host cells as well as members of the microbiota resulting in chronic infections. Nematode interactions with host cells and the microbial environment are prominently mediated by parasite-secreted proteins and peptides possessing immunomodulatory and antimicrobial activities. Previously, we discovered the C-type lectin protein AsCTL-42 in the secreted products of adult Ascaris worms. Here we tested recombinant AsCTL-42 for its ability to interact with bacterial and host cells. We found that AsCTL-42 lacks bactericidal activity but neutralized bacterial cells without killing them. Treatment of bacterial cells with AsCTL-42 reduced invasion of intestinal epithelial cells by Salmonella. Furthermore, AsCTL-42 interacted with host myeloid C-type lectin receptors. Thus, AsCTL-42 is a parasite protein involved in the triad relationship between Ascaris, host cells, and the microbiota.

The ceramide moiety of disialoganglioside (GD3) is essential for GD3 recognition by the sialic acid-binding lectin SIGLEC7 on the cell surface.

To analyze the binding specificity of a sialic acid-recognizing lectin, sialic acid-binding Ig-like lectin 7 (SIGLEC7), to disialyl gangliosides (GD3s), here we established GD3-expressing cells by introducing GD3 synthase (GD3S or ST8SIA1) cDNA into a colon cancer cell line, DLD-1, that expresses no ligands for the recombinant protein SIGLEC7-Fc. SIGLEC7-Fc did not recognize newly-expressed GD3 on DLD-1 cells, even though GD3 was highly expressed, as detected by an anti-GD3 antibody. Because milk-derived GD3 could be recognized by this fusion protein when incorporated onto the surface of DLD-1 cells, we compared the ceramides in DLD-1-generated and milk-derived GD3s to identify the SIGLEC7-specific GD3 structures on the cell membrane, revealing that SIGLEC7 recognizes only GD3-containing regular ceramides but not phytoceramides. This was confirmed by knockdown/knockout of the sphingolipid delta(4)-desaturase/C4-monooxygenase (DES2) gene, involved in phytoceramide synthesis, disclosing that DES2 inhibition confers SIGLEC7 binding. Furthermore, knocking out fatty acid 2-hydroxylase also resulted in the emergence of SIGLEC7 binding to the cell surface. To analyze the effects of binding between SIGLEC7 and various GD3 species on natural killer function, we investigated cytotoxicity of peripheral blood mononuclear cells from healthy donors toward GD3S-transfected DLD-1 (DLD-1-GD3S) cells and DLD-1-GD3S cells with modified ceramides. We found that cytotoxicity is suppressed in DLD-1-GD3S cells with dehydroxylated GD3s. These results indicate that the ceramide structures in glycosphingolipids affect SIGLEC7 binding and distribution on the cell surface and influence cell sensitivity to killing by SIGLEC7-expressing effector cells.

Glucan Binding Protein C of Streptococcus mutans Mediates both Sucrose-Independent and Sucrose-Dependent Adherence.

The high-resolution structure of glucan binding protein C (GbpC) at 1.14 Å, a sucrose-dependent virulence factor of the dental caries pathogen Streptococcus mutans, has been determined. GbpC shares not only structural similarities with the V regions of AgI/II and SspB but also functional adherence to salivary agglutinin (SAG) and its scavenger receptor cysteine-rich domains (SRCRs). This is not only a newly identified function for GbpC but also an additional fail-safe binding mechanism for S. mutans Despite the structural similarities with S. mutans antigen I/II (AgI/II) and SspB of Streptococcus gordonii, GbpC remains unique among these surface proteins in its propensity to adhere to dextran/glucans. The complex crystal structure of GbpC with dextrose (ß-d-glucose; Protein Data Bank ligand BGC) highlights exclusive structural features that facilitate this interaction with dextran. Targeted deletion mutant studies on GbpC's divergent loop region in the vicinity of a highly conserved calcium binding site confirm its role in biofilm formation. Finally, we present a model for adherence to dextran. The structure of GbpC highlights how artfully microbes have engineered the lectin-like folds to broaden their functional adherence repertoire.

Pallidin is a novel interacting protein for cytohesin-2 and regulates the early endosomal pathway and dendritic formation in neurons.

Cytohesin-2 is a member of the guanine nucleotide exchange factors for ADP ribosylation factor 1 (Arf1) and Arf6, which are small GTPases that regulate membrane traffic and actin dynamics. In this study, we first demonstrated that cytohesin-2 localized to the plasma membrane and vesicles in various subcellular compartment in hippocampal neurons by immunoelectron microscopy. Next, to understand the molecular network of cytohesin-2 in neurons, we conducted yeast two-hybrid screening of brain cDNA libraries using cytohesin-2 as bait and isolated pallidin, a component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) involved in endosomal trafficking. Pallidin interacted specifically with cytohesin-2 among cytohesin family members. Glutathione S-transferase pull-down and immunoprecipitation assays further confirmed the formation of a protein complex between cytohesin-2 and pallidin. Immunofluorescence demonstrated that cytohesin-2 and pallidin partially colocalized in various subsets of endosomes immunopositive for EEA1, syntaxin 12, and LAMP2 in hippocampal neurons. Knockdown of pallidin or cytohesin-2 reduced cytoplasmic EEA1-positive early endosomes. Furthermore, knockdown of pallidin increased the total dendritic length of cultured hippocampal neurons, which was rescued by co-expression of wild-type pallidin but not a mutant lacking the ability to interact with cytohesin-2. In contrast, knockdown of cytohesin-2 had the opposite effect on total dendritic length. The present results suggested that the interaction between pallidin and cytohesin-2 may participate in various neuronal functions such as endosomal trafficking and dendritic formation in hippocampal neurons. Cover Image for this issue: doi: 10.1111/jnc.14197.

An overview of lectin-glycan interactions: a key event in initiating fungal infection and pathogenesis.

Infections due to microfungi are of serious concern in many parts of the world. Many species of microfungi are known to cause systemic infection in human beings. Pathogenic microorganisms employ various molecular strategies for colonizing a susceptible host. Recent studies have shown the importance of lectins from microfungi that enable the pathogen to interact with the host, resulting in host immune response. These fungal lectins or adhesins show specific affinities to the glycans present on the membrane proteins or lipids. Binding of the pathogen to the receptors, probably toll-like receptors or dectins, present on the host cell surface triggers/initiates a cascade of signalling pathways, leading to the activation of transcription factors such as NF-κB resulting in the release of proinflammatory cytokines which in turn recruit cells of the immune system to the site of microbial insult to combat the pathogen or resulting in pathogenesis. In this review, we will focus on the interaction between fungal lectins and the host glycans initiating pathogenesis and how the host immune system tries to suppress the pathogenesis.

DCPP1 is the mouse ortholog of human PAUF that possesses functional analogy in pancreatic cancer.

Pancreatic adenocarcinoma upregulated factor (PAUF) overexpressed in pancreatic ductal adenocarcinoma (PDAC) plays a major role in tumor progression and metastasis by autocrine and paracrine manners. However, underlying molecular mechanism of PAUF functioning in pancreatic cancer are not fully understood yet. The objective of this study was to evaluate the potential of demilune cell and parotid protein 1 (DCPP1) as a putative mouse ortholog of human PAUF by sequence alignment and functional studies. Overexpression of mouse DCPP1 in Chinese hamster ovary (CHO) cells or pancreatic cancer cells increased cell proliferation, migration, invasion, and adhesion ability in vitro. Treatment of human pancreatic cancer cells with recombinant mouse DCPP1 elevated cell growth, motility, invasiveness, and adhesiveness. Mouse DCPP1 exerted its function on pancreatic cancer cells by activating intracellular signaling pathways involved in aggressive cancer phenotype of human pancreatic cancer cells. Moreover, subcutaneous injection of mice with DCPP1-overexpressing CHO cells increased tumor sizes. Taken together, we conclude that mouse DCPP1 is a multifunctional promoter of tumor growth through functional activation of pancreatic cancer cells, suggesting it to be an ortholog of human PAUF.

Defective release of α granule and lysosome contents from platelets in mouse Hermansky-Pudlak syndrome models.

Hermansky-Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, bleeding diathesis, and other variable symptoms. The bleeding diathesis has been attributed to δ storage pool deficiency, reflecting the malformation of platelet dense granules. Here, we analyzed agonist-stimulated secretion from other storage granules in platelets from mouse HPS models that lack adaptor protein (AP)-3 or biogenesis of lysosome-related organelles complex (BLOC)-3 or BLOC-1. We show that α granule secretion elicited by low agonist doses is impaired in all 3 HPS models. High agonist doses or supplemental adenosine 5'-diphosphate (ADP) restored normal α granule secretion, suggesting that the impairment is secondary to absent dense granule content release. Intravital microscopy following laser-induced vascular injury showed that defective hemostatic thrombus formation in HPS mice largely reflected reduced total platelet accumulation and affirmed a reduced area of α granule secretion. Agonist-induced lysosome secretion ex vivo was also impaired in all 3 HPS models but was incompletely rescued by high agonist doses or excess ADP. Our results imply that (1) AP-3, BLOC-1, and BLOC-3 facilitate protein sorting to lysosomes to support ultimate secretion; (2) impaired secretion of α granules in HPS, and to some degree of lysosomes, is secondary to impaired dense granule secretion; and (3) diminished α granule and lysosome secretion might contribute to pathology in HPS.

Mitogenic lectins from Cephalosporium curvulum (CSL) and Aspergillus oryzae (AOL) mediate host-pathogen interactions leading to mycotic keratitis.

A core-fucose-specific lectin, CSL from Cephalosporium curvulum, has been reported earlier. Here we assign the role for CSL and another lectin AOL, from pathogenic fungus Aspergillus oryzae, in causing mycotic keratitis. CSL and AOL show strong binding to immortalized and primary human corneal epithelial cells (HCECs) which are inhibited by asialofetuin, confirming their glycan-mediated binding. CSL and AOL showed increase in viability at lower concentrations (0.07 µg/ml) whereas at higher concentrations (0.15 µg/ml and 0.30 µg/ml), have inhibitory effect on immortalized HCECs. Lectin-mediated effect was comparable with the effect induced by the Colony Forming Units (CFUs) of C. curvulum and A. oryzae. CFUs induced more than 1.5-fold increase in HCECs proliferation. Both lectins and fungal CFUs induce secretion of proinflammatory cytokines IL6 and IL8 implicated in ocular diseases. This was supported by upregulation of TLR2 and 4 by lectins as revealed by flow cytometry and RT-PCR. CSL and AOL mediate host-pathogen interactions leading to mycotic keratitis. The mechanism of pathogenesis is possibly initiated through surface binding of mycelia through the lectins to TLR2/4 followed by upregulation of proinflammatory cytokines IL6, IL8 and TLR2 and 4. Understanding the mechanism of pathogenesis is of clinical significance in designing and developing therapeutic strategy to control the infection.

Adipose-derived protein omentin prevents neointimal formation after arterial injury.

Obesity is highly linked with the development of vascular diseases. Omentin is a circulating adipokine that is downregulated in patients with cardiovascular diseases. In this study, we investigated the role of omentin in regulation of vascular remodeling in response to injury. Wild-type (WT) mice were treated intravenously with adenoviral vectors encoding human omentin (Ad-OMT) or control ß-gal and subjected to arterial wire injury. Ad-OMT treatment reduced the neointimal thickening and the frequencies of bromodeoxyuridine-positive proliferating cells in injured arteries. Treatment of vascular smooth muscle cells (VSMCs) with human omentin protein at a physiologic concentration led to suppression of growth and ERK phosphorylation after stimulation with various growth factors. Omentin stimulated AMPK signaling in VSMCs, and blockade of AMPK reversed omentin-mediated inhibition of VSMC growth and ERK phosphorylation. Furthermore, fat-specific human omentin transgenic (OMT-TG) mice exhibited reduced neointimal thickening and vascular cell growth following vascular injury. AMPK activation was enhanced in injured arteries in OMT-TG mice, and administration of AMPK inhibitor reversed the reduction of neointimal hyperplasia in OMT-TG mice. These data indicate that omentin attenuates neointimal formation after arterial injury and suppresses VSMC growth through AMPK-dependent mechanisms. Thus, omentin can represent a novel target molecule for the prevention of vascular disorders.

Modulatory Role of Omentin-1 in Inflammation: Cytokines and Dietary Intake.

PURPOSE: Obesity is known as a chronic inflammatory state whereby anti-inflammatory adipokines, such as omentin-1 levels, are decreased. The present study aims to determine omentin-1 levels in relation to dietary intake, inflammation, and immune response in healthy obese individuals. METHOD: A total of 170 obese participants (body mass index [BMI] ≥ 30) were recruited in this cross-sectional study. Body composition was evaluated by a body composition analyzer, and inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], interleukin (IL)-4, IL-6, IL-1ß, IL-17, IL-10, IL-13, and tumor necrosis factor-alpha [TNF-α]) were measured by enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: We observed associations between higher serum levels of omentin-1 and lower levels of fasting insulin, glucose, total cholesterol, IL-6, and TNF-α concentrations; higher levels of IL-13, IL-4, and IL-1ß were associated with higher serum levels of omentin-1 (all p < 0.05). Omentin-1 levels were not associated with IL-10, hs-CRP, and IL-17 concentrations. We also observed associations between higher intake of saturated fatty acid (SFA) and omentin-1 levels, even after adjustment for total energy intake (p = 0.04). Women with low intake of SFA had higher levels of omentin-1 (p = 0.03); a similar relation was not observed in men. CONCLUSION: Omentin-1 has an anti-inflammatory role in obesity and exerts its effects probably by inducing an increase in Th-2 cytokines comprising IL-13 and IL-4. Omentin-1 is not related to IL-17, a regulatory T cell cytokine, which modulates T helper balance. Levels of inflammatory cytokines are decreased in higher concentrations of omentin-1, except IL-1ß. Lower intake of SFA may modify omentin-1 levels in women. Our study demonstrated the probable protective role of omentin-1 in obesity-related inflammation and insulin resistance.

Multifunctional role of ß-1, 3 glucan binding protein purified from the haemocytes of blue swimmer crab Portunus pelagicus and in vitro antibacterial activity of its reaction product.

ß-1, 3 glucan binding protein (ß-GBP) was isolated from the haemocytes of blue swimmer crab, Portunus pelagicus and purified by laminarin coupled Sephadex G-100 affinity column chromatography. The purified ß-GBP has the molecular mass of 100 kDa, confirmed by SDS-PAGE. The X-ray diffraction analysis of purified ß-GBP indicates the crystalline nature of the protein and also the presence of single peak confirming the existence of ß-glucan molecule. The results of agglutination assay showed that the purified ß-GBP had the ability to agglutinate with yeast cell, Saccharomyces cerevisiae and mammalian erythrocytes. ß-GBP can agglutinate with yeast cells at the concentration of 50 µg/ml. The phagocytic and encapsulation activity of purified ß-GBP from P. pelagicus was determined with yeast cell S. cerevisiae and sepharose bead suspension respectively. This reveals that, ß-GBP have the ability to detect the pathogen associated molecular patterns (PAMP) found on the surface of fungi and bacteria. The recognition of invading foreign substances and in the involvement of functional activities induces the activation of prophenoloxidase. This revealed that ß-GBP play a major role in the innate immune system of crustaceans by stimulating the prophenoloxidase system. Moreover, it was obvious to note that ß-GBP reaction product exhibited antibacterial and antibiofilm activity against Gram positive and Gram negative bacteria. This study concludes the functional aspects of ß-GBP purified from P. pelagicus and its vital role in the stimulation of prophenoloxidase cascade during the pathogenic infection.

Siglecs induce tolerance to cell surface antigens by BIM-dependent deletion of the antigen-reactive B cells.

Infusion of blood cells from a donor can induce humoral tolerance in a recipient and increase the probability of successful organ transplant, a clinical method defined as donor-specific transfusion (DST). Despite the clinical success of DST, the immunological mechanisms by which blood cells displaying a foreign Ag induce tolerance remain poorly understood. Based on recent findings showing that the B cell siglecs, CD22 and Siglec-G, can promote tolerance to Ags presented on the same surface as their ligands, we speculated that the B cell siglecs are key players in tolerance induced by DST. Using a variety of chemical and genetic approaches, we show that the B cell siglecs mediate tolerance to cell surface Ags by initiating an inhibitory signal that culminates in elimination of the Ag-reactive B cell. CD22 and Siglec-G are recruited to the immunological synapse by sialic acid ligands on the Ag-bearing cells, producing a tolerogenic signal involving Lyn and the proapoptotic factor BIM that promotes deletion of the B cell and failure of mice to develop Abs to the Ag upon subsequent challenge. We speculate that this tolerogenic mechanism is a contributing factor in DST and a mechanism of peripheral B cell tolerance to cell surface autoantigens.

Siglec-10 is associated with survival and natural killer cell dysfunction in hepatocellular carcinoma.

BACKGROUND: The interaction between Siglec-10 and its ligand, CD24, selectively represses tissue damage-caused immune responses. However, the nature of Siglec-10 and CD24 in human hepatocellular carcinoma (HCC) is still poorly defined. Hereon, the expression, function, and regulation of CD24 and Siglec-10 in HCC were investigated in the present study. METHODS: Flow cytometry was performed to examine the expression of Siglec-10 in HCC tissues and adjacent non-tumor tissues of HCC patients. To further determine whether Siglec-10 expression is associated with the clinical characteristics and survival, conventional immunohistochemistry was performed in 96 HCC patients. Additionally, the role of Siglec-10 in the regulation of natural killer (NK) cell dysfunction was evaluated. Finally, CD24 expression in HCC was also assessed. RESULTS: Siglec-10 was expressed most on NK cells in HCC (40.7 ± 4.5%). Compared with surrounding non-tumor tissues, tumor tissues had higher Siglec-10 expression (31.0 ± 1.7% versus 40.7 ± 4.5%, n = 10, P < 0.05), and the expression was negatively associated with patient survival. Siglec-10(+)CD56(+) NK cells exhibited reduced effector function, as shown by decreased granules and cytokine expressions compared with Siglec-10(-)CD56(+) NK cells. Moreover, the number of CD24(+)CD45(-) cells in HCC tissues was higher than that in adjacent non-tumor tissues (9.4 ± 0.9% versus 3.1 ± 0.9%, n = 15, P < 0.05). CONCLUSIONS: These findings suggest that Siglec-10 is associated with decreased survival and impaired NK cell function in human HCC. This process may function via the CD24-Siglec-10 interaction, which may represent a therapeutic target in HCC patients.

YKL-40 induces IL-8 expression from bronchial epithelium via MAPK (JNK and ERK) and NF-κB pathways, causing bronchial smooth muscle proliferation and migration.

Recently, the serum levels of YKL-40, a chitinase-like glycoprotein, have been shown to be significantly elevated in asthmatics and are associated with asthma severity. Although these studies raise the possibility that YKL-40 may influence asthma, the mechanisms remain unknown. This study firstly investigated the mechanisms involved in YKL-40-mediated inflammation in human bronchial epithelial cells (HBECs) and analyzed the soluble factors secreted by bronchial epithelial cells exposed to YKL-40 that were responsible for increasing proliferation and migration of primary normal human bronchial smooth muscle cells (BSMCs). YKL-40-induced inflammation was assayed in two HBECs (BEAS-2B cell line and primary HBECs). In addition, we treated BEAS-2B cells and HBECs with YKL-40 and added the conditioned culture media to BSMCs. The proliferation and migration of BSMCs were determined by premixed WST-1 cell proliferation reagent (Clontech Laboratories) and QCM chemotaxis migration assay (Millipore), respectively. Bronchial epithelial cells treated with YKL-40 resulted in a significant increase of IL-8 production, which was dependent on MAPK (JNK and ERK) and NF-κB pathways activation. YKL-40-induced IL-8 was found to further stimulate proliferation and migration of BSMCs, and the effects were inhibited after neutralizing IL-8. Through investigating the interaction of airway epithelium and smooth muscle, our findings implicate that YKL-40 may be involved in the inflammation of asthma by induction of IL-8 from epithelium, subsequently contributing to BSMC proliferation and migration. Moreover, inhibition of IL-8 signaling is a potential therapeutic target for YKL-40-induced inflammation and remodeling of asthma.

Lectin-Based Profiling of Coelomocytes in Holothuria scabra and Expression of Superoxide Dismutase in Purified Coelomocytes.

Coelomocytes are the first line of immune defense in marine animals. Their distributions are greatly variable even in the close animal species. In this study, we used lectin staining to aid in the classification and purification of these cells for further investigation of SOD distribution among coelomocytes of H. scraba. We classified coelomocytes into four types: type 1, lymphocytes; type 2, phagocytes; type 3, spherulocytes; and type 4, giant cells. Among four lectins used, Con A appeared to give a broad reactivity against most coelomocytes, except for giant cells. In addition, phagocytes usually engaged the highest fluorescent intensity with most lectins, with the exception of PNA, for which spherulocytes possessed the highest fluorescent intensity. Using FACS for fraction collection, it was found that F1 fraction contained the purest phagocyte population (> 95%), which was highly reactive with anti- superoxide dismutase (SOD) as revealed by immunoblotting and immunofluorescence staining, although some minor staining was also detected in spherulocytes. Our results thus provide a fundamental platform for comparing alterations that may happen to the population and SOD contents of coelomocytes when the sea cucumber is subjected to environmental changes that would activate their immune responses.

Evolution of the lectin-complement pathway and its role in innate immunity.

Discrimination between self and non-self by lectins (carbohydrate-binding proteins) is a strategy of innate immunity that is found in both vertebrates and invertebrates. In vertebrates, immune recognition mediated by ficolins (lectins that consist of a fibrinogen-like and a collagen-like domain), as well as by mannose-binding lectins, triggers the activation of the complement system, which results in the activation of novel serine proteases. The presence of a similar lectin-based complement system in ascidians, our closest invertebrate relatives, indicates that the complement system probably had a pivotal role in innate immunity before the evolution of an adaptive immune system in jawed vertebrates.

C-type lectin receptors on dendritic cells and Langerhans cells.

Dendritic cells and Langerhans cells are specialized for the recognition of pathogens and have a pivotal role in the control of immunity. As guardians of the immune system, they are present in essentially every organ and tissue, where they operate at the interface of innate and acquired immunity. Recently, several C-type lectin and lectin-like receptors have been characterized that are expressed abundantly on the surface of these professional antigen-presenting cells. It is now becoming clear that lectin receptors not only serve as antigen receptors but also regulate the migration of dendritic cells and their interaction with lymphocytes.

Role of chitin and chitinase/chitinase-like proteins in inflammation, tissue remodeling, and injury.

The 18 glycosyl hydrolase family of chitinases is an ancient gene family that is widely expressed from prokaryotes to eukaryotes. In mammals, despite the absence of endogenous chitin, a number of chitinases and chitinase-like proteins (C/CLPs) have been identified. However, their roles have only recently begun to be elucidated. Acidic mammalian chitinase (AMCase) inhibits chitin-induced innate inflammation; augments chitin-free, allergen-induced Th2 inflammation; and mediates effector functions of IL-13. The CLPs BRP-39/YKL-40 (also termed chitinase 3-like 1) inhibit oxidant-induced lung injury, augments adaptive Th2 immunity, regulates apoptosis, stimulates alternative macrophage activation, and contributes to fibrosis and wound healing. In accord with these findings, levels of YKL-40 in the lung and serum are increased in asthma and other inflammatory and remodeling disorders and often correlate with disease severity. Our understanding of the roles of C/CLPs in inflammation, tissue remodeling, and tissue injury in health and disease is reviewed below.