Recombinant Human Mannose Binding Lectin (RHMBL) Dampens The Inflammatory Response Of Human Alveolar Macrophages To Influenza A Virus In Vitro

Mannose-binding lectin (MBL) is a circulating protein that acts as a soluble pattern recognition molecule of the innate immunity. It binds to carbohydrate patterns on the surface of pathogens or of altered self-cells, with activation of the lectin pathway of the complement system. Recent evidence indicates that MBL contributes to the pathophysiology of ischemia-reperfusion injury and other conditions. Thus, MBL inhibitors offer promising therapeutic strategies, since they prevent the interaction of MBL with its target sugar arrays. We developed and characterized a novel assay based on surface plasmon resonance for in vitro screening of these compounds, which may be useful before the more expensive and time-consuming in vivo studies. The assay measures the inhibitor’s ability to interfere with the binding of murine MBL-A or MBL-C, or of human recombinant MBL, to mannose residues immobilized on the sensor chip surface. We have applied the assay to measure the IC50 of synthetic glycodendrimers, two of them with neuroprotective properties in animal models of MBL-mediated injuries.

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Mannose-Binding Lectin in Severe Acute Respiratory Syndrome Coronavirus Infection

The Journal of Infectious Diseases ◽

10.1086/429631 ◽

2005 ◽

Vol 191 (10) ◽

pp. 1697-1704 ◽

Cited By ~ 133

Author(s):

W. K. Eddie Ip ◽

Kwok Hung Chan ◽

Helen K. W. Law ◽

Gloria H. W. Tso ◽

Eric K. P. Kong ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Serum Levels ◽

Mannose Binding Lectin ◽

In Vitro Assays ◽

Calcium Dependent ◽

Control Subjects ◽

Mannose Binding ◽

Carbohydrate Recognition Domains ◽

Binding Lectin

Abstract Little is known about the innate immune response to severe acute respiratory syndrome (SARS) coronavirus (CoV) infection. Mannose-binding lectin (MBL), a key molecule in innate immunity, functions as an ante-antibody before the specific antibody response. Here, we describe a case-control study that included 569 patients with SARS and 1188 control subjects and used in vitro assays to investigate the role that MBL plays in SARS-CoV infection. The distribution of MBL gene polymorphisms was significantly different between patients with SARS and control subjects, with a higher frequency of haplotypes associated with low or deficient serum levels of MBL in patients with SARS than in control subjects. Serum levels of MBL were also significantly lower in patients with SARS than in control subjects. There was, however, no association between MBL genotypes, which are associated with low or deficient serum levels of MBL, and mortality related to SARS. MBL could bind SARS-CoV in a dose- and calcium-dependent and mannan-inhibitable fashion in vitro, suggesting that binding is through the carbohydrate recognition domains of MBL. Furthermore, deposition of complement C4 on SARS-CoV was enhanced by MBL. Inhibition of the infectivity of SARS-CoV by MBL in fetal rhesus kidney cells (FRhK-4) was also observed. These results suggest that MBL contributes to the first-line host defense against SARS-CoV and that MBL deficiency is a susceptibility factor for acquisition of SARS

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