Disease relevance of PRF1

• RESULTS: Resembling the effects of CTL derived lytic granules, perforin caused gradual myocyte shortening and contracture, leading to complete loss of the rod shaped morphology and to cell destruction [1].
• Damage to myocytes by infiltrating cytotoxic lymphocytes, containing lytic granules and the pore-forming protein, perforin, thereof, probably contribute to the immunological rejection of the transplanted heart, to autoimmune diseases and possibly to congestive heart failure associated with myocarditis [2].

High impact information on PRF1

• Cells with cytotoxic activity against the cell line K562 and expressing perforin have been demonstrated in endometrial cells isolated from pigs early in pregnancy [3].
• Elevated cytotoxic effector molecule expression (Fas ligand, perforin, granzyme B) indicates T-cell mediated graft destruction by cytotoxic and cytolytic mechanisms within 48 to 72 h after transplantation [4].
• Fas ligand, perforin and granzyme B transcripts were all elevated at 48 and 72 h post-transplant [4].
• NK lysis of pEC was abrogated by concanamycin A and ammonium chloride, reagents inhibiting the perforin/granzyme B (grB) pathway, but only partially blocked by caspase inhibition with z-VAD-fmk [5].
• To clarify the participation of perforin/granzymescell mediated cytotoxicity (P/G-CMC), when EGTA or concanamycin B (CMB) was added to the cytotoxicity assays, both cytotoxicities were completely inhibited by these drugs in a dose-dependent manner [6].

Biological context of PRF1

• To address one important aspect of heart transplant rejection, we investigated in guinea pig ventricular myocytes how CTL-derived lytic granules containing the pore-forming protein perforin reduce the membrane potential (VM) and cause cell damage [7].

Anatomical context of PRF1

• Granzyme A alone was ineffective, but accelerated the deleterious effects of perforin on the morphological and electrophysiological properties of myocytes [1].
• NK effector cells were isolated from each endometrial sample, size fractionated and tested for cytolytic activity against NK target cells (K562) using chromium release assays and immunocytochemically for the frequency of perforin-positive cells [8].
• Perforin expression can define CD8 positive lymphocyte subsets in pigs allowing phenotypic and functional analysis of natural killer, cytotoxic T, natural killer T and MHC un-restricted cytotoxic T-cells [9].
• Perforin was expressed in subpopulations of both CD8alphaalpha and CD8alphabeta lymphocytes, but was not expressed in gammadelta T-cells or monocyte/macrophages [9].

Associations of PRF1 with chemical compounds

• The aim of the study was to investigate how CTL derived perforin, the serine protease granzyme A, and the combination of both, damage guinea pig ventricular myocytes [1].
• However, the requirement for divalent cation differed from that for perforin-induced lysis, since the microsome-mediated lysis occurred in the presence of EDTA [10].

Regulatory relationships of PRF1

• Perforin positive lymphocytes expressed both CD2 and CD8alpha, most were small dense lymphocytes (SDL) and up to 90% were CD3 negative [9].
• The remaining perforin positive lymphocytes were large and granular and contained more CD3+CD5+CD6+ T-cells (-40%) of which a substantial proportion also co-expressed CD4 [9].

References