Cationic protein granulysin (GNLY) is produced by activated human cytotoxic T lymphocytes (CTL) and natural killer (NK) cells (Pena SV et al. 1997; Stenger S et al. 1998; Ogawa K et al. 2003). GNLY can target extracellular and intracelullar pathogens. It is believed that the electrostatic interaction between the cationic GNLY and the negatively charged microbial cell surface increases the ability of GNLY to fold into amphipathic conformation which can disrupt microbial membranes resulting in cytolysis by osmotic shock (Wang Z et al. 2000; Ernst WA et al. 2000; Anderson DH et al. 2003; Barman H et al. 2006).
GNLY is synthesized as a 15-kDa molecule and then proteolytically cleaved at the amino and carboxyl termini to produce a 9-kDa form (Pena SV et al. 1997; Hanson DA et al. 1999). The 9?-kDa form of GNLY is confined to cytolytic granules that are directionally released by receptor-mediated granule exocytosis following target cell recognition (Hanson DA et al. 1999; Clayberger C et al 2012). In contrast, the 15-kDa form is constitutively secreted from distinct granules that lack perforin and granzyme (Clayberger C et al 2012). The 9-kDa GNLY exhibits cytolytic activity on the numerous microbes ranging from extracellular and intracellular bacteria to fungi and parasite (Stenger S et al. 1998; Ernst WA et al. 2000). GNLY kills Mycobacterium tuberculosis, the causative agent in tuberculosis and Plasmodium falciparum, a cause of malaria (Stenger S et al. 1998; Farouk SE et al. 2004). Alongside its ability to kill bacteria, fungi, and parasites, GNLY can block viral replication and trigger apoptosis in infected cells (Hata A et al. 2001).
Besides its direct antimicrobial activity, GNLY shows tumoricidal activity by inducing apoptosis in tumor cells. Both 9-kDA and 15-kDA forms of GNLY may also function as chemoattractants for T lymphocytes, monocytes and other inflammatory cells and activates the expression of a number of cytokines (Deng A et al. 2005; Castiello L et al. 2011).