title: The biology of cytotoxic cell granule exocytosis pathway: granzymes have evolved to induce cell death and inflammation.
abstract: The granule exocytosis pathway of cytotoxic lymphocytes (Tc and NK cells) is critical for control of tumor development and viral infections. Granule-associated perforin and granzymes are key components in Tc cell-mediated function(s). On the basis of studies that showed granzymes A, B, C, K and M, to induce apoptosis in vitro, all granzymes were thought to also induce cell death in vivo. This review summarizes our present understanding of the biological processes elicited by purified granzyme A and granzyme as well as the processes induced by the more physiologically relevant cytotoxic cells secreting these proteases. The combined evidence supports the concept that the granule secretion pathway is not mono-specific but rather poly-functional including induction of pro-inflammatory cytokines, besides their widely appreciated apoptotic properties.
authors.affiliation: Dpto. Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Pardo
authors.forename: Juan Ignacio
authors.initials: JI
authors.lastname: Aguilo
authors.forename: Alberto
authors.initials: A
authors.lastname: Anel
authors.forename: Praxedis
authors.initials: P
authors.lastname: Martin
authors.forename: Lars
authors.initials: L
authors.lastname: Joeckel
authors.forename: Christoph
authors.initials: C
authors.lastname: Borner
authors.forename: Reiner
authors.initials: R
authors.lastname: Wallich
authors.forename: Arno
authors.initials: A
authors.lastname: Müllbacher
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Froelich
authors.forename: Markus M
authors.initials: MM
authors.lastname: Simon
mesh_terms: D016923:Cell Death; D005089:Exocytosis / Q000502:physiology*; D053804:Granzymes / Q000633:toxicity*; D007249:Inflammation; D007694:Killer Cells, Natural / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D053804:Granzymes