Analysis of granulysin-mediated cytotoxicity in peripheral blood of patients with psoriatic arthritis
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The objective of the present study was to investigate possible changes in granulysin (GNLY)-mediated cytotoxicity of peripheral blood lymphocytes in psoriatic arthritis (PsA) patients with respect to different phases of the disease. We prospectively enrolled 25 PsA patients in the active phase, 26 PsA patients in remission and 24 healthy controls. The simultaneous detection of intracellular GNLY and cell surface antigens (CD3 and CD56) was performed with flow cytometry. GNLY apoptotic protein was visualised by immunocytochemistry. Natural killer (NK) cell cytotoxicity was analysed with a cytotoxicity assay against human erythroleukaemia K-562 cells. The percentage of GNLY+ cells did not differ significantly between PsA patients in the acute phase and those in remission; however, it was always higher than in healthy examinees due to the increased percentage of GNLY+ cells within T cells, NKT cells, and both, and in the CD56+dim and CD56+bright NK subsets. The mean fluorescence intensity for GNLY was higher in all lymphocyte subpopulations in the acute phase than in remission and in healthy controls. Accordingly, GNLY-mediated NK cell cytotoxicity against K-562 cells of active phase PsA patients was significantly higher than that in patients in remission or in healthy controls. These findings demonstrated the involvement of GNLY in the worsening of PsA and suggested that GNLY mediated the development of joint lesions.
KeywordsCell-mediated cytotoxicity Cytotoxic T lymphocytes Granulysin Natural killer cells Psoriasis Psoriatic arthritis
This work was supported by the Special Hospital for Medical Rehabilitation of Heart and Lung Diseases and Rheumatism ‘Thalassotherapia-Opatija’, Opatija, Croatia, and a grant from the Croatian Ministry of Science (No. 062-620402-0377).
Conflict of interest
The authors declare that they have no conflict of interest.
- 12.Prpić L, Strbo N, Sotosek V, Gruber F, Podack ER, Rukavina D (2000) Assessment of perforin expression in peripheral blood lymphocytes in psoriatic patients during exacerbation of disease. Acta Derm Venereol Suppl (Stockh) 211:14–16Google Scholar
- 17.Yawalkar N, Hunger RE, Buri C, Schmid S, Egli F, Brand CU, Mueller C, Pichler WJ, Braathen LR (2001) A comparative study of the expression of cytotoxic proteins in allergic contact dermatitis and psoriasis: spongiotic skin lesions in allergic contact dermatitis are highly infiltrated by T cells expressing perforin and granzyme B. Am J Pathol 158:803–808PubMedCrossRefGoogle Scholar
- 34.Metkar SS, Wang B, Aguilar-Santelises M, Raja SM, Uhlin-Hansen L, Podack E, Trapani JA, Froelich CJ (2002) Cytotoxic cell granule-mediated apoptosis: perforin delivers granzyme B-serglycin complexes into target cells without plasma membrane pore formation. Immunity 16:417–428PubMedCrossRefGoogle Scholar
- 36.Kaspar AA, Okada S, Kumar J, Poulain FR, Drouvalakis KA, Kelekar A, Hanson DA, Kluck RM, Hitoshi Y, Johnson DE, Froelich CJ, Thompson CB, Newmeyer DD, Anel A, Clayberger C, Krensky AM (2001) A distinct pathway of cell-mediated apoptosis initiated by granulysin. J Immunol 167:350–356PubMedGoogle Scholar