Cytotoxic cell granule-mediated apoptosis

Perforin delivers granzyme b-serglycin complexes into target cells without plasma membrane pore formation

Sunil S. Metkar, Baikun Wang, Miguel Aguilar-Santelises, Srikumar M. Raja, Lars Uhlin-Hansen, Eckhard Podack, Joseph A. Trapani, Christopher J. Froelich

Research output: Contribution to journalArticle

195 Citations (Scopus)

Abstract

The mechanism underlying perforin (PFN)-dependent delivery of apoptotic granzymes during cytotoxic cell granule-mediated death remains speculative. Granzyme B (GrB) and perforin were found to coexist as multimeric complexes with the proteoglycan serglycin (SG) in cytotoxic granules, and cytotoxic cells were observed to secrete exclusively macromolecular GrB-SG. Contrary to the view that PFN acts as a gateway for granzymes through the plasma membrane, monomeric PFN and, strikingly, PFN-SG complexes were shown to mediate cytosolic delivery of macromolecular GrB-SG without producing detectable plasma membrane pores. These results indicate that granule-mediated apoptosis represents a phenomenon whereby the target cell perceives granule contents as a multi meric complex consisting of SG, PFN, and granzymes, which are, respectively, the scaffold, translocator, and targeting/informational components of this modular delivery system.

Original languageEnglish
Pages (from-to)417-428
Number of pages12
JournalImmunity
Volume16
Issue number3
DOIs
StatePublished - Apr 9 2002
Externally publishedYes

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Granzymes
Perforin
Cell Membrane
Apoptosis
Proteoglycans
serglycin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Metkar, S. S., Wang, B., Aguilar-Santelises, M., Raja, S. M., Uhlin-Hansen, L., Podack, E., ... Froelich, C. J. (2002). Cytotoxic cell granule-mediated apoptosis: Perforin delivers granzyme b-serglycin complexes into target cells without plasma membrane pore formation. Immunity, 16(3), 417-428. https://doi.org/10.1016/S1074-7613(02)00286-8

Cytotoxic cell granule-mediated apoptosis : Perforin delivers granzyme b-serglycin complexes into target cells without plasma membrane pore formation. / Metkar, Sunil S.; Wang, Baikun; Aguilar-Santelises, Miguel; Raja, Srikumar M.; Uhlin-Hansen, Lars; Podack, Eckhard; Trapani, Joseph A.; Froelich, Christopher J.

In: Immunity, Vol. 16, No. 3, 09.04.2002, p. 417-428.

Research output: Contribution to journalArticle

Metkar, SS, Wang, B, Aguilar-Santelises, M, Raja, SM, Uhlin-Hansen, L, Podack, E, Trapani, JA & Froelich, CJ 2002, 'Cytotoxic cell granule-mediated apoptosis: Perforin delivers granzyme b-serglycin complexes into target cells without plasma membrane pore formation', Immunity, vol. 16, no. 3, pp. 417-428. https://doi.org/10.1016/S1074-7613(02)00286-8
Metkar, Sunil S. ; Wang, Baikun ; Aguilar-Santelises, Miguel ; Raja, Srikumar M. ; Uhlin-Hansen, Lars ; Podack, Eckhard ; Trapani, Joseph A. ; Froelich, Christopher J. / Cytotoxic cell granule-mediated apoptosis : Perforin delivers granzyme b-serglycin complexes into target cells without plasma membrane pore formation. In: Immunity. 2002 ; Vol. 16, No. 3. pp. 417-428.
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