Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Granulysin is a newly identified CTL/NK cell-related cytotoxic protein, which is secreted in both constitutive and Ca-dependent manner. To evaluate its significance in stem-cell transplantation (SCT), serum granulysin was measured by newly established ELISA method in 26 patients undergoing SCT (21 allogeneic and 5 autologous). In the allogeneic SCT, granulysin was transiently increased in 3 weeks, which was not observed in autologous SCT. In acute GVHD, serum granulysin was markedly increased and correlated with the severity of GVHD. Elevation of granulysin was not necessarily associated with increase of sIL2R or IFN-gamma. In vitro, allospecific T cells released granulysin in an allo-specific manner, and it was correlated with allo-specific cytotoxic activity. These results indicate that increased release of granulysin presents alloreactivity and serum granulysin is useful as a marker of GVHD in SCT.
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PMID:Analysis of serum granulysin in patients with hematopoietic stem-cell transplantation: its usefulness as a marker of graft-versus-host reaction. 1662 30

Graft-versus-host disease (GVHD) is an important complication of bone marrow transplantation and is known to induce sweat gland abnormalities. We employed immunohistochemical staining for granulysin, dermcidin as well as IL-17 and Foxp3 in the lesional skin of 7 patients with acute GVHD. Granulysin-bearing cells were distributed in the epidermis, basal membrane zone of the dermis, and superficial perivascular lesion of the dermis. Interestingly, granulysin-bearing cells were also detected around the secretory portion of the eccrine glands, which might be related to the downregulation of the expression of dermcidin on the secretory portion of the eccrine glands. Differing from a mouse model, in human acute GVHD, IL-17-producing cells and Foxp3(+) cells were not prominent. Our present observation sheds light on the contribution of granulysin-bearing cells to the decrease of the sweat in patients with acute GVHD. Though we did not assess the function of these infiltrating lymphocytes directly, further analysis of the mechanism of this phenomenon would offer fundamental insight into the establishment of acute GVHD.
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PMID:Granulysin-Bearing Cells in the Skin Lesions of Acute Graft-versus-Host Disease: Possible Mechanisms for Hypohidrosis in Graft-versus-Host Disease. 2362 47

Granulysin, a cationic protein expressed by human natural killer cells and cytotoxic T lymphocytes, is a mediator for drug-induced Stevens-Johnson syndrome and graft-versus-host disease. Some 15 kDa granulysin are processed into 9 kDa forms and sequestered in cytolytic granules, while others are constitutively secreted into body fluids. Both 9 and 15 kDa granulysin have been shown to be a serum marker for cell-mediated immunity. Furthermore, 15 kDa is able to activate monocyte differentiation. However, its antimicrobial properties have not been clearly addressed. Here, we report a novel method to prepare both the soluble 9 and 15 kDa granulysin and show that the 15 kDa form is more effective than the 9 kDa form in exerting specific antimicrobial activity against Pseudomonas aeruginosa within a range of few micromolars. We also show that the 15 kDa granulysin is able to hyperpolarize the membrane potential and increase membrane permeability of treated bacteria. Interestingly, the bactericidal activity and membrane permeability of the granulysins were markedly reduced at lower pH (pH 5.4) as a result of probable increase in hydrophobicity of the granulysins. Additionally, we've also shown the granulysin to inhibit biofilm formation by P. aeruginosa. These results suggest that the 15 kDa granulysin exhibits a novel mechanism in bacteria killing in a way that's different from most antimicrobial peptides. Our novel granulysin preparation methodology will be useful for further study of action mechanisms of other antimicrobial, cytotoxic and immunomodulating properties in granulysin-mediated diseases.
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PMID:Antimicrobial Properties of an Immunomodulator - 15 kDa Human Granulysin. 2727 51