A significant difference was also observed in the median mRNA expression of the
perforin gene: 362 and 52.8 mRNA relative units, respectively, for patients with and without acute rejection (Mann-Whitney; P=0.001).
Cytotoxic cell granule-mediated apoptosis:
perforin delivers granzyme B-serglycin complexes into target cells without plasma membrane pore formation.
The abnormal NK cells were positive for surface CD45 (high), CD2, CD26, CD38, CD94 (high), and HLA-DR and cytoplasmic granzyme B and
perforin; and they were negative for surface CD3, CD4, CD5, CD7, CD8, CD11c, CD16, CD19, CD20, CD25, CD56, Ig kappa, and lambda chains.
Interestingly, despite having a lower expression of
perforin and granzyme (GZM) B, the mRNA expression of these proteins are high [100].
Konjevic, "Decreased expression of NKG2D, NKp46, DNAM-1 receptors, and intracellular
perforin and STAT-1 effector molecules in NK cells and their dim and bright subsets in metastatic melanoma patients," Melanoma Research, vol.
These C2 domains are identified in the current study with their Protein Data Bank (PDB) entry and correspond to cPL[A.sub.2] (1RLW),
perforin (3W57), Munc13-1 (3KWU), Car4 (5A50 and 4V29), Car4 (5A52), PKC[alpha] (1DSY), PKC[beta] (1[A.sub.2]5), rabphilin-3A (2K3H and 2CM5), Synaptotagmin-1 C2A (1BYN), and C2B (1UOV), SV2A (4V11), and Synaptotagmin-7 C2B (3N5A).
There is coexistence of immune dysregulation with unchecked inflammation.11 Mutations of
perforin gene, are seen in 20 to 30% of FLH patients.12
Moreover, recent research has also revealed the third pathway, called the
perforin pathway, which involves T-cell mediated cytotoxicity and is induced by granzyme B protein.
In primary HLH, dysfunction mutations in the genes encoding
perforin, Munc13-4, syntaxinll protein play a role in etiopathogenesis.
The genes encodes the protein normally involved in killing or eliminating abnormal immune cells or proteins which facilitate the delivery of
perforin to the cells which are to be killed.
(d) PRF1,
perforin 1 (pore forming protein); UNC13D, unc-13 homolog D (C.
Perforin and granzyme pathway are initiated by
perforin which open the way for granzyme to cause cell death.
