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Granzyme A (GrA) has long been recognized as one of the key players in the induction of cell death of neoplastic, foreign or infected cells after granule delivery by cytotoxic cells. While the cytotoxic potential of GrA is controversial in current literature, accumulating evidence now indicates roles for extracellular GrA in modulating inflammation and inflammatory diseases. This paper aims to explore the literature presenting current knowledge on GrA as an extracellular modulator of inflammation by summarizing (i) the presence and role of extracellular GrA in several inflammatory diseases, and (ii) the potential molecular mechanisms of extracellular GrA in augmenting inflammation. [ABSTRACT FROM AUTHOR]

• Toxoplasma introduces ROP and GRA effectors into host cells to coopt host functions. • ROP effector secretion occurs during invasion via an unknown mechanism. • MYR1-3, ROP17, and ASP5 are required for transit of GRAs across Toxoplasma 's PVM. • Plasmodium employs different machinery (PTEX) to transport GRAs across the PVM. • Translocation of effector proteins into host cells by Toxoplasma gondii. The Apicomplexan parasite, Toxoplasma gondii, is an obligate intracellular organism that must co-opt its host cell to survive. To this end, Toxoplasma parasites introduce a suite of effector proteins from two secretory compartments called rhoptries and dense granules into the host cells. Once inside, these effectors extensively modify the host cell to facilitate parasite penetration, replication and persistence. In this review, we summarize the most recent advances in current understanding of effector translocation from Toxoplasma 's rhoptry and dense granule organelles into the host cell, with comparisons to Plasmodium spp. for broader context. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells are cytotoxic lymphocytes that are present in the circulation but also in many organs including spleen and gut, where they play an important role in the defense against infections. Interaction of NK cells with target cells leads to degranulation, which results in the release of perforin and granzymes in the direct vicinity of the target cell. Chicken NK cells have many characteristics similar to their mammalian counterparts and based on similarities with studies on human NK cells, surface expression of CD107 was always presumed to correlate with granule release. However, proof of this degranulation or in fact the actual presence of perforin (PFN) and granzyme A (GrA) in chicken NK cells and their release upon activation is lacking. Therefore, the purpose of the present study was to determine the presence of perforin and granzyme A in primary chicken NK cells and to measure their release upon degranulation, as an additional tool to study the function of chicken NK cells. Using human specific antibodies against PFN and GrA in fluorescent and confocal microscopy resulted in staining in chicken NK cells. The presence of PFN and GrA was also confirmed by Western blot analyses and its gene expression by PCR. Stimulation of NK cells with the pectin SPE6 followed by flow cytometry resulted in reduced levels of intracellular PFN and GrA, suggesting release of PFN and GrA. Expression of PFN and GrA reversely correlated with increased surface expression of the lysosomal marker CD107. Finally it was shown that the supernatant of activated NK cells, containing the NK cell granule content including PFN and GrA, was able to kill Escherichia coli. This study correlates PFN and GrA release to activation of chicken NK cells and establishes an additional tool to study activity of cytotoxic lymphocytes in chickens. • Chicken NK cells express perforin and granzyme A proteins. • Perforin and Granzyme A are localized in intracellular granular-compartments. • Flow cytometry can measure release of intracellular perforin and granzyme A. • Intracellular perforin and granzyme A content are reversely correlated to surface expression of CD107. [ABSTRACT FROM AUTHOR]