Mast cell proteoglycans

Abstract

Mast cells are versatile effector cells of the immune system, contributing to both innate and adaptive immunity toward pathogens but also having profound detrimental activities in the context of inflammatory disease. A hallmark morphological feature of mast cells is their large content of cytoplasmic secretory granules, filled with numerous secretory compounds, including highly negatively charged heparin or chondroitin sulfate proteoglycans of serglycin type. These anionic proteoglycans provide the basis for the strong metachromatic staining properties of mast cells seen when applying various cationic dyes. Functionally, the mast cell proteoglycans have been shown to have an essential role in promoting the storage of other granule-contained compounds, including bioactive monoamines and different mast cell-specific proteases. Moreover, granule proteoglycans have been shown to regulate the enzymatic activities of mast cell proteases and to promote apoptosis. Here, the current knowledge of mast cell proteoglycans is reviewed.

Figure 1.

Proteoglycans of serglycin type are essential for the metachromatic staining properties of mast cells. Cytospin slides were prepared from wild-type (WT) (A) and serglycin^–/– (B) bone marrow–derived mast cells and were stained with May Grünwald/Giemsa. Note the characteristic strong metachromatic, granular staining of wild-type cells and the lack of corresponding staining in cells lacking serglycin. Size bars: 50 µm.

Figure 2.

Functions of granule proteoglycans (serglycin) in mast cells. In non-activated mast cells, serglycin is located within secretory granules and promotes the storage of various proteases and biogenic amines (histamine, serotonin, dopamine). Note the tetrameric organization of tryptase, which is dependent on the interaction with serglycin. Note also that certain granule compounds are stored independently of serglycin (e.g., β-hexosaminidase). When mast cells degranulate, serglycin is released. During this process, certain compounds may be detached from serglycin (e.g., histamine), whereas others remain attached. As depicted, serglycin-protease complexes may bind to the mast cell surface after degranulation. If the granule membrane is damaged, fully active proteases in complex with serglycin enter the cytosol and can cause apoptosis. GAG, glycosaminoglycan.