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Neutral serine proteases of neutrophils
Author(s) -
Kettritz Ralph
Publication year - 2016
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12441
Subject(s) - proteases , proteinase 3 , biology , autoimmunity , serine , neutrophil extracellular traps , serine protease , autoantibody , immunology , inflammation , microbiology and biotechnology , enzyme , biochemistry , protease , immune system , antibody
Summary Neutrophil serine proteases ( NSP s) exercise tissue‐degrading and microbial‐killing effects. The spectrum of NSP ‐mediated functions grows continuously, not least because of methodological progress. Sensitive and specific FRET substrates were developed to study the proteolytic activity of each NSP member. Advanced biochemical methods are beginning to characterize common and specific NSP substrates. The resulting novel information indicates that NSP s contribute not only to genuine inflammatory neutrophil functions but also to autoimmunity, metabolic conditions, and cancer. Tight regulatory mechanisms control the proteolytic potential of NSP s. However, not all NSP functions depend on their enzymatic activity. Proteinase‐3 ( PR 3) is somewhat unique among the NSP s for PR 3 functions as an autoantigen. Patients with small‐vessel vasculitis develop autoantibodies to PR 3 that bind their target antigens on the neutrophil surface and trigger neutrophil activation. These activated cells subsequently contribute to vascular necrosis with life‐threatening multiorgan failure. This article discusses various aspects of NSP biology and highlights translational aspects with strong clinical implications.