Eosinophil granule major basic protein 1 (MBP1)

Eosinophil granule major basic protein 1 (MBP1), encoded by the PRG2 gene, is a highly basic, arginine-rich protein that serves as the primary constituent of the crystalline core of eosinophil granules [2.2.1, 2.2.2]. It is synthesized as a non-toxic pro-form (proMBP1) and undergoes proteolytic cleavage to its mature, cytotoxic form during storage in the granule [2.2.2, 3.2.3]. MBP1 is a potent cytotoxin and helminthotoxin that plays a vital role in the innate immune response against parasites and microbes by disrupting their cell membranes through electrostatic interactions [2.4.1, 3.2.1]. However, its release during eosinophil degranulation is also a major driver of host tissue damage in inflammatory and allergic diseases, such as asthma, eosinophilic esophagitis, and atopic dermatitis [2.4.1, 2.5.4]. In these conditions, MBP1 causes epithelial exfoliation, bronchial hyperreactivity, and triggers the release of inflammatory mediators from mast cells and basophils [2.2.1, 3.1.5]. Therapeutic strategies targeting MBP1 include the use of heparin-like molecules, such as gleceparin sodium (NTX-1024), which bind and neutralize the protein's toxic effects [3.2.2, 3.3.1]. Direct neutralization of MBP1 represents a novel approach to mitigating eosinophil-mediated pathology, potentially offering a more targeted alternative to systemic eosinophil depletion [3.3.1, 3.3.2].

Other names

PRG2Proteoglycan 2Bone marrow proteoglycanEosinophil major basic proteinproMBPBMPG

Neutralization of the protein's high positive charge and inhibition of its cytotoxic aggregation, thereby preventing membrane disruption and subsequent host tissue damage.