Mechanisms of eosinophil degranulation: PH regulation and release of Major Basic Protein (MBP)

Jennifer L. Bankers-Fulbright, Scott M. O'Grady

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The release of pre-formed granule proteins is a fundamental characteristic of eosinophil activation. Upon release, these granule proteins have toxic effects on parasite and mammalian host cells and tissues. Release of secondary (crystalloid) granule proteins from an activated eosinophil requires trafficking of the granule or granule-derived vesicles to the plasma membrane followed by discharge of the contents. Unlike granule proteins that are stored in the fluid matrix of the granule, eosinophil major basic protein (MBP) is present as a crystalline core. This crystalline core is composed primarily of MBP associated with a negatively charged scaffold protein and is insoluble at physiological pH. However, the observed release, deposition, and function of MBP in vitro and in vivo are consistent with eosinophil discharge of soluble MBP. Thus, the conversion of MBP from a crystalline structure to a soluble protein is a necessary initial step in eosinophil activation and function. Our research indicates that eosinophil activation signals which increase intracellular [Ca2+] cause a dramatic rise in cytoplasmic pH temporally associated with secondary granule acidification. Because the crystalline core is soluble at low pH, we propose that activation-induced granule acidification is the key mechanism that allows eosinophils to discharge soluble MBP. In this chapter we present our findings with those of others to summarize the current understanding of degranulation and MBP release.

Original languageEnglish (US)
Title of host publicationEosinophils
Subtitle of host publicationStructure, Biological Properties and Role in Disease
PublisherNova Science Publishers, Inc.
Pages25-46
Number of pages22
ISBN (Electronic)9781611222708
ISBN (Print)9781619426412
StatePublished - Dec 1 2013

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