Biogenesis and secretory pathways of mast cell chymase: structural and functional aspects

Abstract

Chymase is a specific protease of mast cells (MC) with variable expression and is one of the preformed components of the secre-tome. Chymase biogenesis begins with the processes of transcription in the nucleus, continuing in the cytoplasm of MC on ribosomes and in the cisterna of the endoplasmic reticulum. Entering the Golgi complex, molecules of the prochymase undergo post-translational modifications, this continuing in the vesicles detached from trans Golgi network. During further processing under granules maturation, chymase becomes an active enzyme and undergoes in-tragranular accumulation with typical topographic regularities, determining the features of the cytological and ultrastructural phenotype of MC. Various secretory mechanisms of chymase excretion into the extracellular matrix result in the development of diverse biological effects due to high selectivity of the protease to the molecular targets of cellular and extracellular components of the specific tissue microenvironment. Since chymase is an important enzyme in the formation of the state of the integrative-buffer metabolic environment of connective tissue, it is advisable to consider it as a diagnostic marker and a probable pharmacological target in the treatment of a number of pathological conditions. The involvement of chymase in the mechanisms of inflammation and allergy, angiogenesis and oncogenesis, remodeling of the extracellular matrix of connective tissue and changes in the histoarchitectonics of organs is also known. The technology of immunohistochemical staining using chro-mogenic or fluorescence detection allows objectively determining the number of chymase-positive MCs in the intraorgan population, the mechanisms of biogenesis and processing, cyto- and histoto-pographic characteristics with visualization of secretory pathways. Thus, the morphological identification of chymase significantly expands the interpretation of the data obtained in the study of adaptive and pathological states of internal organs, claiming not only diagnostic value, but also an assessment of the therapy performed.