Antimicrobial peptides (AMPs) are small molecules produced by a myriad of cells and play important roles not only in protecting against infections and sustaining skin barrier homeostasis but also in contributing to immune dysregulation under pathological conditions. Recently, increasing evidence has indicated that AMPs, including cathelicidin (LL-37), human β-defensins, S100 proteins, lipocalin 2, and RNase 7, are highly expressed in psoriatic skin lesions. These peptides broadly regulate immunity by interacting with various immune cells and linking innate and adaptive immune responses during the progression of psoriasis. In this review, we summarize the recent findings regarding AMPs in the pathogenesis of psoriasis with a main focus on their immunomodulatory abilities.
Adaptive Immunity ; Humans ; Immunity, Innate ; Pore Forming Cytotoxic Proteins ; Psoriasis ; Skin Diseases ; beta-Defensins

Cytotoxic T cell (CTL) covers several subtypes, which are CD8+, CD4 and CD4-CD8-. CTL derives from T cell repertoire in lymphoid hematopoietic stem cells. It matures in thymus and is activated in peripheral lymphoid tissues. Effector CTL kills the target cells by 2 ways. One is apoptotic effect mediated by FasL-Fas pathway and the other one is cytolytic effect mediated by granzymes. CTL has aroused great attention due to its significance in anti-tumor and anti-virus.
Animals ; Fas Ligand Protein ; Humans ; Membrane Glycoproteins ; immunology ; Perforin ; Pore Forming Cytotoxic Proteins ; T-Lymphocytes, Cytotoxic ; immunology ; fas Receptor ; immunology

Humans ; Pyroptosis/physiology* ; Pore Forming Cytotoxic Proteins

The hinge structure, also known as hinge region or bend, is a special structure found in some antimicrobial peptides. Most studies on antimicrobial peptides focused on the standard secondary structure of α-helix and β-sheet, while the hinge structure and its functions were rarely studied. The hinge structure confers the antimicrobial peptides an improved structural flexibility, which may promote their disruptive effect on bacterial membrane or their binding efficiency to the intracellular targets, thus resulting in a higher antibacterial activity. Meanwhile, the hinge structure may reduce the structural rigidity, which may eliminate the cytotoxicity of antimicrobial peptides to eukaryotic cells. This article reviews the structural characteristics of the hinge structure, its effects on the biological activity of antimicrobial peptides and application in the molecular design, with the aim to provide a reference for the design and development of new antimicrobial peptides.
Anti-Bacterial Agents/pharmacology* ; Anti-Infective Agents/pharmacology* ; Antimicrobial Cationic Peptides/pharmacology* ; Pore Forming Cytotoxic Proteins ; Protein Structure, Secondary

Granzyme is an effector molecule of activated cytotoxic T cells and natural killer cells. It mainly mediates cell apoptosis. Its function could be explained by its molecular characteristics to some extent. Its cytotoxic effect is related to some other factors contributing to apoptosis induction. It deserves studying if perforin mediates entrance of granzyme into cells. As potential substrates of granzyme caspases and their substrates have been paid much attention to.
Animals ; Apoptosis ; Caspases ; immunology ; Granzymes ; Humans ; Killer Cells, Natural ; immunology ; Membrane Glycoproteins ; immunology ; Perforin ; Pore Forming Cytotoxic Proteins ; Serine Endopeptidases ; immunology ; T-Lymphocytes, Cytotoxic ; immunology

DNA Mutational Analysis ; Diagnosis, Differential ; Humans ; Lymphohistiocytosis, Hemophagocytic ; diagnosis ; genetics ; therapy ; Mutation ; genetics ; Perforin ; Pore Forming Cytotoxic Proteins ; genetics ; Qa-SNARE Proteins ; genetics

<b>OBJECTIVEb>To study the roles of granzyme B and perforin in diagnosing acute rejection after liver transplantation, and the relationship between their activity index (AI) and Banff's histological grading criteria.

<b>METHODSb>Liver biopsies were processed as for routine surgical specimens and labeled with granzyme B and perforin monoclonal antibodies. The number of positive cells/mm(2) was determined as activity index (AI) by IPP image analysis software. Histologic findings were used as the "gold standard" in diagnosing acute rejection.

<b>RESULTSb>Of 41 liver biopsy samples studied, acute rejection was noted in 21 cases, the remaining 20 cases showed no evidence of rejection. The AI of granzyme B and perforin in the acute rejection group was significantly higher than that in the non-acute rejection group (< 0.001). In the acute rejection group, the AI in moderate to severe acute rejection was higher than that in mild to indeterminate acute rejection (< 0.001). Compared with the "golden" histologic criteria, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of granzyme B in diagnosing acute rejection were 90.0%, 95.2%, 94.7%, 90.9% and 92.7% respectively. The values of these parameters for perforin were also above 80%.

<b>CONCLUSIONSb>Granzyme B and perforin are key markers of activated immune cells in acute rejection and highly expressed during acute liver rejection episodes. As ancillary investigations, these parameters demonstrated high sensitivity and specificity in diagnosing acute rejection in allograft post-transplant liver biopsies.

Biomarkers ; Biopsy ; Graft Rejection ; diagnosis ; metabolism ; Granzymes ; metabolism ; Humans ; Liver ; metabolism ; pathology ; Liver Transplantation ; immunology ; Membrane Glycoproteins ; metabolism ; Perforin ; Pore Forming Cytotoxic Proteins ; metabolism ; Sensitivity and Specificity

<b>OBJECTIVEb>To investigate the expression of perforin and granzyme B in rejection response following liver transplantation, and evaluate their roles to be used as predictive markers of rejection.

<b>METHODSb>The expression of perforin and granzyme B in liver biopsies obtained from liver allograft recipients was determined by immunohistochemistry. Biopsies were classified into two groups-no evidence of rejection and rejection-according to Histopathologic criteria. The relationship between the perforin/granzume B expression and acute rejection was analyzed.

<b>RESULTSb>From 19 patients, thirty-five liver biopsies were obtained after liver transplantation. Among them, nineteen samples were diagnosed as rejection response. The frequencies of perforin and granzyme B expression in rejection group were 100% (19/19) and 94.7% (18/19), respectively. While those in no rejection group were 25.0% (4/16) and 12.5 (2/16), respectively. In most rejected samples, perforin and granzyme B were expressed simultaneously. Only three samples showed perforin expression alone, while no samples demonstrated granzyme B expression alone. There was a close relationship between perforin/granzyme B expression and liver allograft rejection.

<b>CONCLUSIONb>Perforin and granzyme B expression seemed to be related to the development of acute rejection following liver transplantation, and might be served as sensitive and reliable markers in diagnosing acute rejection in early stage.

Adult ; Biomarkers ; Female ; Graft Rejection ; diagnosis ; metabolism ; Granzymes ; Humans ; Liver Cirrhosis ; surgery ; Liver Neoplasms ; surgery ; Liver Transplantation ; immunology ; Male ; Membrane Glycoproteins ; biosynthesis ; genetics ; Middle Aged ; Perforin ; Pore Forming Cytotoxic Proteins ; Serine Endopeptidases ; biosynthesis ; genetics ; T-Lymphocytes, Cytotoxic ; enzymology

Perforin and granzyme are important effector molecules in cytolytic cells. They can induce apoptosis of tumor cells and infection cells. The research of biologic missile is noticed with the progress in therapy targeting to the disease. It is supposed that perforin and granzyme play an important role in biological missiles because of their biologic function and structure. A review on several aspects of these effector molecules is presented.
Animals ; Granzymes ; Humans ; Killer Cells, Natural ; immunology ; Membrane Glycoproteins ; immunology ; therapeutic use ; Neoplasms ; immunology ; therapy ; Perforin ; Pore Forming Cytotoxic Proteins ; Serine Endopeptidases ; immunology ; therapeutic use ; T-Lymphocytes, Cytotoxic ; immunology

The study was aimed to investigate the etiology and the clinical characteristics of patients with hemophagocytic syndrome. The clinical data of 38 patients with hemophagocytic syndrome were retrospectively analyzed, and prf1 and stx11 were detected for the mutational analysis. The results showed that 38 cases were diagnosed as hemophagocytic syndrome, including 1 case of familial hemophagocytic lymphohistiocytosis (FHL), 14 cases associated with infectious disease (36.84%), 10 cases with malignancies (26.32%), 7 cases with rheumatic disease (18.42%), other 6 cases of unknown etiology (15.79%). 9 out of 38 cases died with mortality of 23.68%, including 4 cases associated with infectious disease, 2 cases with malignancies, 1 case with rheumatic disease, and 2 cases of unknown etiology. One case was found to have prf1 mutation, and was diagnosed as FHL at last. It is concluded that the causes of HPS are diverse, different etiology results in different outcome. It is important to find etiology when HPS is diagnosed, and prf1 and stx11 genetic analysis plays a important role in the diagnosis of FHL.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; DNA Mutational Analysis ; Exons ; Female ; Humans ; Lymphohistiocytosis, Hemophagocytic ; etiology ; genetics ; Male ; Middle Aged ; Perforin ; Pore Forming Cytotoxic Proteins ; genetics ; Qa-SNARE Proteins ; genetics ; Retrospective Studies ; Young Adult