Abstract
This study was undertaken to determine the effect of Pseudomonas aeruginosa alkaline protease (AP) and elastase (ELA) on human lymphocyte function. AP at 50 micrograms/ml and ELA at 12 micrograms/ml caused a 50% inhibition of phytohemagglutinin-induced proliferation. There was no difference in the effect of proteases on CD4- and CD8-positive cells. To determine the effect of proteases on interleukin-2 (IL-2)-induced cell proliferation, the proteases and IL-2 were added to the IL-2-dependent CTLL-2 cell line. AP and ELA inhibited the proliferation of these cells. When IL-2 was added in excess, the inhibition was partly reversed. ELA at 10 micrograms/ml cleaved IL-2, as judged by size chromatography of a reaction mixture containing 125I-labeled IL-2 and the proteases. The ELA-digested IL-2 exhibited a reduced binding capacity to IL-2 receptors on the lymphocytes. Furthermore, treatment of phytohemagglutinin-stimulated lymphocytes with AP and ELA resulted in inhibition of binding of intact IL-2 to IL-2 receptors on the stimulated lymphocytes. These results indicated that P. aeruginosa-derived enzymes are able to interfere with human lymphocyte function in vitro and that this effect might be due to cleavage of IL-2.
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- Blackwood L. L. Decreased delayed-type hypersensitivity and increased protection to Listeria monocytogenes seen in mice infected with mucoid and nonmucoid Pseudomonas aeruginosa. Infect Immun. 1985 Mar;47(3):840–842. doi: 10.1128/iai.47.3.840-842.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blackwood L. L., Lin T., Rowe J. I. Suppression of the delayed-type hypersensitivity and cell-mediated immune responses to Listeria monocytogenes induced by Pseudomonas aeruginosa. Infect Immun. 1987 Mar;55(3):639–644. doi: 10.1128/iai.55.3.639-644.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blackwood L. L., Stone R. M., Iglewski B. H., Pennington J. E. Evaluation of Pseudomonas aeruginosa exotoxin A and elastase as virulence factors in acute lung infection. Infect Immun. 1983 Jan;39(1):198–201. doi: 10.1128/iai.39.1.198-201.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carney S. A., Dyster R. E., Jones R. J. The invasion of burned skin by Pseudomonas aeruginosa. Br J Dermatol. 1973 Jun;88(6):539–545. doi: 10.1111/j.1365-2133.1973.tb08016.x. [DOI] [PubMed] [Google Scholar]
- Colizzi V., Garzelli C., Campa M., Falcone G. Depression of contact sensitivity by enhancement of suppressor cell activity in Pseudomonas aeruginosa-injected mice. Infect Immun. 1978 Aug;21(2):354–359. doi: 10.1128/iai.21.2.354-359.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Diaz E., Mosovich L. L., Neter E. Serogroups of Pseudomonas aeruginosa and the immune response of patients with cystic fibrosis. J Infect Dis. 1970 Mar;121(3):269–274. doi: 10.1093/infdis/121.3.269. [DOI] [PubMed] [Google Scholar]
- Döring G., Dalhoff A., Vogel O., Brunner H., Dröge U., Botzenhart K. In vivo activity of proteases of Pseudomonas aeruginosa in a rat model. J Infect Dis. 1984 Apr;149(4):532–537. doi: 10.1093/infdis/149.4.532. [DOI] [PubMed] [Google Scholar]
- Döring G., Obernesser H. J., Botzenhart K. Extrazelluläre Toxine von Pseudomonas aeruginosa. II. Einwirkung zweier gereinigter Proteasen auf die menschlichen Immunoglobuline IgG, IgA und sekretorisches IgA. Zentralbl Bakteriol A. 1981 Mar;249(1):89–98. [PubMed] [Google Scholar]
- Floersheim G. L., Hopff W. H., Gasser M., Bucher K. Impairment of cell-mediated immune responses by Pseudomonas aeruginosa. Clin Exp Immunol. 1971 Aug;9(2):241–247. [PMC free article] [PubMed] [Google Scholar]
- Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
- Gray L., Kreger A. Microscopic characterization of rabbit lung damage produced by Pseudomonas aeruginosa proteases. Infect Immun. 1979 Jan;23(1):150–159. doi: 10.1128/iai.23.1.150-159.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holt P. S., Misfeldt M. L. Alteration of murine immune response by Pseudomonas aeruginosa exotoxin A. Infect Immun. 1984 Jul;45(1):227–233. doi: 10.1128/iai.45.1.227-233.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holt P. S., Misfeldt M. L. Variables which affect suppression of the immune response induced by Pseudomonas aeruginosa exotoxin A. Infect Immun. 1986 Apr;52(1):96–100. doi: 10.1128/iai.52.1.96-100.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Issekutz T. B., Stoltz J. M. Suppression of lymphocyte proliferation by Pseudomonas aeruginosa: mediation by Pseudomonas-activated suppressor monocytes. Infect Immun. 1985 Jun;48(3):832–838. doi: 10.1128/iai.48.3.832-838.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kharazmi A., Döring G., Høiby N., Valerius N. H. Interaction of Pseudomonas aeruginosa alkaline protease and elastase with human polymorphonuclear leukocytes in vitro. Infect Immun. 1984 Jan;43(1):161–165. doi: 10.1128/iai.43.1.161-165.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kharazmi A., Eriksen H. O., Döring G., Goldstein W., Høiby N. Effect of Pseudomonas aeruginosa proteases on human leukocyte phagocytosis and bactericidal activity. Acta Pathol Microbiol Immunol Scand C. 1986 Oct;94(5):175–179. doi: 10.1111/j.1699-0463.1986.tb02108.x. [DOI] [PubMed] [Google Scholar]
- Kharazmi A., Høiby N., Döring G., Valerius N. H. Pseudomonas aeruginosa exoproteases inhibit human neutrophil chemiluminescence. Infect Immun. 1984 Jun;44(3):587–591. doi: 10.1128/iai.44.3.587-591.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Meuer S. C., Hussey R. E., Fabbi M., Fox D., Acuto O., Fitzgerald K. A., Hodgdon J. C., Protentis J. P., Schlossman S. F., Reinherz E. L. An alternative pathway of T-cell activation: a functional role for the 50 kd T11 sheep erythrocyte receptor protein. Cell. 1984 Apr;36(4):897–906. doi: 10.1016/0092-8674(84)90039-4. [DOI] [PubMed] [Google Scholar]
- Morihara K., Tsuzuki H., Oda K. Protease and elastase of Pseudomonas aeruginosa: inactivation of human plasma alpha 1-proteinase inhibitor. Infect Immun. 1979 Apr;24(1):188–193. doi: 10.1128/iai.24.1.188-193.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nishino N., Powers J. C. Pseudomonas aeruginosa elastase. Development of a new substrate, inhibitors, and an affinity ligand. J Biol Chem. 1980 Apr 25;255(8):3482–3486. [PubMed] [Google Scholar]
- Parmely M. J., Horvat R. T. Antigenic specificities of Pseudomonas aeruginosa alkaline protease and elastase defined by human T cell clones. J Immunol. 1986 Aug 1;137(3):988–994. [PubMed] [Google Scholar]
- Parmely M. J., Iglewski B. H., Horvat R. T. Identification of the principal T lymphocyte-stimulating antigens of Pseudomonas aeruginosa. J Exp Med. 1984 Nov 1;160(5):1338–1349. doi: 10.1084/jem.160.5.1338. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pavlovskis O. R., Wretlind B. Assessment of protease (elastase) as a Pseudomonas aeruginosa virulence factor in experimental mouse burn infection. Infect Immun. 1979 Apr;24(1):181–187. doi: 10.1128/iai.24.1.181-187.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pedersen B. K., Kharazmi A. Inhibition of human natural killer cell activity by Pseudomonas aeruginosa alkaline protease and elastase. Infect Immun. 1987 Apr;55(4):986–989. doi: 10.1128/iai.55.4.986-989.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pedersen B. K., Kharazmi A., Theander T. G., Odum N., Andersen V., Bendtzen K. Selective modulation of the CD4 molecular complex by Pseudomonas aeruginosa alkaline protease and elastase. Scand J Immunol. 1987 Jul;26(1):91–94. doi: 10.1111/j.1365-3083.1987.tb02239.x. [DOI] [PubMed] [Google Scholar]
- Petit J. C., Richard G., Burghoffer B., Daguet G. L. Suppression of cellular immunity to Listeria monocytogenes by activated macrophages: mediation by prostaglandins. Infect Immun. 1985 Aug;49(2):383–388. doi: 10.1128/iai.49.2.383-388.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robb R. J., Munck A., Smith K. A. T cell growth factor receptors. Quantitation, specificity, and biological relevance. J Exp Med. 1981 Nov 1;154(5):1455–1474. doi: 10.1084/jem.154.5.1455. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rubin H. R., Sorensen R. U., Chase P. A., Klinger J. D. Suppression of in vitro lymphocyte DNA synthesis by killed Pseudomonas aeruginosa. Infect Immun. 1983 Feb;39(2):630–637. doi: 10.1128/iai.39.2.630-637.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schultz D. R., Miller K. D. Elastase of Pseudomonas aeruginosa: inactivation of complement components and complement-derived chemotactic and phagocytic factors. Infect Immun. 1974 Jul;10(1):128–135. doi: 10.1128/iai.10.1.128-135.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Snell K., Holder I. A., Leppla S. A., Saelinger C. B. Role of exotoxin and protease as possible virulence factors in experimental infections with Pseudomonas aeruginosa. Infect Immun. 1978 Mar;19(3):839–845. doi: 10.1128/iai.19.3.839-845.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sorensen R. U., Klinger J. D., Cash H. A., Chase P. A., Dearborn D. G. In vitro inhibition of lymphocyte proliferation by Pseudomonas aeruginosa phenazine pigments. Infect Immun. 1983 Jul;41(1):321–330. doi: 10.1128/iai.41.1.321-330.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Woods D. E., Cryz S. J., Friedman R. L., Iglewski B. H. Contribution of toxin A and elastase to virulence of Pseudomonas aeruginosa in chronic lung infections of rats. Infect Immun. 1982 Jun;36(3):1223–1228. doi: 10.1128/iai.36.3.1223-1228.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]