Short Communication: Predicting receptor for mannose-binding lectin on neutrophil surface

Neutrophils play as major phagocytes that participate in the various effector phase of immunity. Mannosebinding lectin (MBL) assisted priming of neutrophils could trigger various processes including modulationof endocytosis rate, reactive oxygen production, chemotaxis, etc., through interactions with cell surfacereceptors. The physiological receptor for MBL on neutrophil's surface is still unreported. Macromoleculardocking could be attempted to determine the protein-protein interactions which are important forunderstanding cellular function and organization. The study was performed to identify the interacting partnerof MBL present on neutrophils surface which leads to the activation of various cell processes. Protein networkanalysis, homology modeling, and Rigid docking were performed to explore structural features and bindingmechanism of MBL with its cellular receptors. The results indicates that CR1 interact with the MBL and mayact as MBL receptor.

Functional estimation of mannose binding lectin associated serine protease (MBL-MASPs) in human serum.

Background & objectives: Mannose binding lectin (MBL), a C-type or Ca2+ dependent lectin, plays a major role in lectin pathway of complement activation. MBL deficiency/insufficiency is associated with susceptibility to many infections. It is important to know the association of functional lectin levels with disease condition. Therefore, we carried out this study to develop a simple assay to estimate the functional MBL-associated serine proteases (MBL-MASPs) levels in human serum samples. Methods: A novel method was developed based on direct haemolysis of mannan coated human erythrocytes in autologous human serum for functional estimation of MBL and associated serine proteases (MBLMASPs complex). Functional MBL-MASPs serum levels in 75 healthy individuals was estimated. Results were compared with those obtained by ELISA based assay. Results: Lysis of mannan coated human RBC in autologous serum was highly specific and mediated by MBL-MASPs lectin complement pathway. Concentration of MBL-MASPs in serum of normal healthy individuals (n=75) was found to be 1.579 μg/ml (median= 1.149 μg/ml) by the haemolytic assay which was comparable to the values obtained by ELISA method. Interpretation & conclusions: Our findings showed that the method developed for the estimation of functional MBL-MASPs levels in human serum is simple, cost-effective and comparable with existing ELISA method.

Disease associations of mannose-binding lectin & potential of replacement therapy.

Mannose-binding lectin (MBL) is an important component of the immune defence able to bind to repeating mannose based structural patterns typical of microbial surface (bacteria, viruses, fungi, parasites) leading to opsonization and phagocytosis, and activation of the complement pathway resulting in lysis of the pathogen. MBL thus plays a very important role in the first line of host immune response. MBL deficiency has been implicated in susceptibility and modulating the severity in viral, bacterial, fungal, and protozoan infections. High MBL levels, on the contrary might be helpful to intracellular organisms, which take the advantage of C3 opsonization and C3 receptor on monocytes/macrophages to enter their host. MBL replacement therapy to help patients with MBL deficiency has undergone phase I clinical trials. Phase II and III trials and production of recombinant MBL for replacement therapy are currently underway.