scholarly journals Therapeutic applications of mannan-binding lectin

2003 ◽  
Vol 25 (4) ◽  
pp. 33-34 ◽  
Author(s):  
David Kilpatrick
Keyword(s):  
Rheumatoid Arthritis ◽  
Cystic Fibrosis ◽  
Innate Immunity ◽  
Bacterial Infections ◽  
Recurrent Miscarriage ◽  
Association Studies ◽  
Disease Association ◽  
Mannan Binding Lectin ◽  
Binding Lectin

Mannan-binding lectin (MBL) is perhaps the best known of the collectins, a subfamily of C-type lectins possessing an additional collagen-like domain. MBL is thought to be an important component of innate immunity. Since the discovery, around 15 years ago, that MBL was identical to a factor responsible for the opsonization of baker's yeast in vitro, a large number of disease-association studies have been conducted. Most of these investigations support the view that MBL can influence susceptibility to, or affect the course of, many diseases. These include bacterial infections, rheumatoid arthritis, cystic fibrosis and recurrent miscarriage. This meeting was arranged to bring together scientists and clinicians to review the clinical significance of MBL, and to consider the most appropriate target disorders for MBL-replacement therapy.

Introduction to mannan-binding lectin

2003 ◽  
Vol 31 (4) ◽  
pp. 745-747 ◽  
Author(s):  
D.C. Kilpatrick
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Deficiency ◽  
Cystic Fibrosis ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Recurrent Miscarriage ◽  
Recombinant Product ◽  
Disease Modifier ◽  
Mannan Binding Lectin ◽  
Binding Lectin

Mannan-binding lectin (MBL) was first discovered as a plasma opsonin for baker's yeast and was independently characterized biochemically. It belongs to the small subfamily of collectins: C-type lectins possessing a collagen-like domain. MBL is synthesized by the liver and secreted into the bloodstream. It is believed to be an important component of innate immunity, acting as an ante-antibody and/or as a disease modifier. It is thought to influence disorders as diverse as meningococcal disease, rheumatoid arthritis, cystic fibrosis and recurrent miscarriage. Lack of MBL may be most relevant in the context of a co-existing secondary immune deficiency. Replacement therapy, first carried out 30 years ago with unfractionated plasma, appears promising. The development of a recombinant product should permit the extension of MBL therapy to randomized clinical trials of sufficient size to provide clear evidence about the physiological significance of this intriguing glycoprotein.

scholarly journals Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules

2021 ◽  
Author(s):  
Matteo Stravalaci ◽  
Isabel Pagani ◽  
Elvezia Maria Paraboschi ◽  
Mattia Pedotti ◽  
Andrea Doni ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Innate Immunity ◽  
Disease Severity ◽  
Fluid Phase ◽  
Systematic Investigation ◽  
In Vitro Models ◽  
Lectin Pathway ◽  
Mannose Binding ◽  
Binding Lectin

The humoral arm of innate immunity includes diverse molecules with antibody-like functions, some of which serve as disease severity biomarkers in COVID-19. The present study was designed to conduct a systematic investigation of the interaction of humoral fluid phase pattern recognition molecules (PRM) with SARS-CoV-2. Out of 10 PRM tested, the long pentraxin PTX3 and Mannose Binding Lectin (MBL) bound the viral Nucleoprotein and Spike, respectively. MBL bound trimeric Spike, including that of variants of concern, in a glycan-dependent way and inhibited SARS-CoV-2 in three in vitro models. Moreover, upon binding to Spike, MBL activated the lectin pathway of complement activation. Genetic polymorphisms at the MBL locus were associated with disease severity. These results suggest that selected humoral fluid phase PRM can play an important role in resistance to, and pathogenesis of, COVID-19, a finding with translational implications.

scholarly journals Mannan Binding Lectin (MBL) genotypes coding for high MBL serum levels are associated with rheumatoid factor negative rheumatoid arthritis in never smokers

2011 ◽  
Vol 13 (2) ◽  
pp. R65 ◽  
Author(s):  
Saedis Saevarsdottir ◽  
Bo Ding ◽  
Kristjan Steinsson ◽  
Gerdur Grondal ◽  
Helgi Valdimarsson ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatoid Factor ◽  
Serum Levels ◽  
Never Smokers ◽  
Mannan Binding Lectin ◽  
Binding Lectin

scholarly journals Abnormal directed migration of blood polymorphonuclear leukocytes in rheumatoid arthritis. Potential role in increased susceptibility to bacterial infections

1998 ◽  
Vol 7 (1) ◽  
pp. 19-23 ◽  
Author(s):  
F. Aglas ◽  
J. Hermann ◽  
G. Egger
Keyword(s):  
Rheumatoid Arthritis ◽  
Polymorphonuclear Leukocytes ◽  
Bacterial Infections ◽  
Membrane Filter ◽  
Absolute Number ◽  
Healthy Controls ◽  
Distribution Characteristic ◽  
Migratory Activity ◽  
Directed Migration

Rheumatoid arthritis (RA) patients are at higher risks of bacterial infection than healthy subjects. Polymorphonuclear leukocytes (PMN) are the first line of nonspecific cellular defence against these infections. We tested the hypothesis that abnormal directed migration of PMN may be one reason for the increased infection rate of RA patients. PMN migration was investigated in 68 peripheral blood samples of 15 RA patients compared with 64 samples of healthy controls in a novel whole bloodin vitromembrane filter assay. The migration of PMNs from RA patients and controls was stimulated using the bacterial chemoattractant N-formyl-methionyl-leucylphenylalanine (fMLP). Unstimulated PMN migration of RA patients was increased compared with healthy controls as measured by the following parameters: (a) absolute number of migrant PMNs (1954 ± 87 vs. 1238 ± 58 PMN/mm2), (b) percentage of PMNs migrated into the filter (total migration index, TMI) (28.6 ± 0.9 vs. 24.0 ± 0.8 %), (c) the distance half the migrating PMNs had covered (distribution characteristic, DC) (22.6 ± 1.1 vs. 16.1 ± 0.6 mm) and (d) the product of TMI and DC (neutrophil migratory activity, NMA) (669.0 ± 45.0 vs. 389.0 ± 18.9). fMLP stimulated PMNs of RA patients showed defective migration compared to unstimulated samples as shown by (a) a reduced number of migrant PMNs (1799 ± 93 PMN/mm2), (b) lower TMI (26.1 ± 0.9 %), (c) unremarkable altered distribution characteristic (22.9 ± 0.8 mm) and (d) significant reduced migratory activity (600.0 ± 30.0). Our data suggest that the high incidence of infections in RA patients may partly be caused by defective migratory activity of PMNs to bacterial chemoattractants as demonstrated by fMLP.

scholarly journals Intrinsic Abnormalities of Cystic Fibrosis Airway Connective Tissue Revealed by an In Vitro 3D Stromal Model

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1371
Author(s):  
Claudia Mazio ◽  
Laura S. Scognamiglio ◽  
Rossella De Cegli ◽  
Luis J. V. Galietta ◽  
Diego Di Bernardo ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Inflammatory Response ◽  
Bacterial Infections ◽  
Inflammatory Cells ◽  
Lung Model ◽  
Lung Dysfunction ◽  
Novel Therapeutic Strategies ◽  
And Function

Cystic fibrosis is characterized by lung dysfunction involving mucus hypersecretion, bacterial infections, and inflammatory response. Inflammation triggers pro-fibrotic signals that compromise lung structure and function. At present, several in vitro cystic fibrosis models have been developed to study epithelial dysfunction but none of these focuses on stromal alterations. Here we show a new cystic fibrosis 3D stromal lung model made up of primary fibroblasts embedded in their own extracellular matrix and investigate its morphological and transcriptomic features. Cystic fibrosis fibroblasts showed a high proliferation rate and produced an abundant and chaotic matrix with increased protein content and elastic modulus. More interesting, they had enhanced pro-fibrotic markers and genes involved in epithelial function and inflammatory response. In conclusion, our study reveals that cystic fibrosis fibroblasts maintain in vitro an activated pro-fibrotic state. This abnormality may play in vivo a role in the modulation of epithelial and inflammatory cell behavior and lung remodeling. We argue that the proposed bioengineered model may provide new insights on epithelial/stromal/inflammatory cells crosstalk in cystic fibrosis, paving the way for novel therapeutic strategies.

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