Degradation of immunoglobulins, protease inhibitors, and interleukin-1 by a secretory proteinase of Acanthamoeba castellanii

The effect of a secretory proteinase from the pathogenic amoebae Acanthamoeba castellanii on hosts defense-oriented or regulatory proteins such as immunoglobulins, interleukin-1, and protease inhibitors was investigated. The enzyme was found to degrade secretory immunoglobulin A (sIgA), IgG, and IgM. It also degraded interleukin-1alpha (IL-1alpha) and IL-1beta. Its activity was not inhibited by endogenous protease inhibitors, such as alpha2-macroglobulin, alpha1-trypsin inhibitor, and alpha2-antiplasmin. Furthermore, the enzyme rapidly degraded those endogenous protease inhibitors as well. The degradation of hosts defense-oriented or regulatory proteins by the Acanthamoeba proteinase suggested that the enzyme might be an important virulence factor in the pathogenesis of Acanthamoeba infection.

Role of proteases in tumor invasion and metastasis.

Cancer remains a major cause of worldwide deaths due to ability of cancer cells to form secondary tumors at other sites by multistep process called metastasis. In order to migrate from their original site, tumor cells have to cross several barriers like basement membranes, interstitial tissues and extracellular matrices, which are composed primarily of collagen, proteoglycans, elastin, laminin and other glycoproteins. Tumor cells over express and secrete proteases which are capable of degrading the components of these barriers and thus facilitate their migration. The classes of proteases which have been implicated in the process of tumor invasion and metastasis include metalloproteases, serine proteases and cathepsins. Cancer cells in general have elevated levels of proteases belonging to more than one class. In some studies, process of invasion has been inhibited by using specific inhibitors of these proteases. Expression of some proteases has been observed only in some specific tumors. These proteases have been proposed to be of diagnostic/prognostic value. However a better understanding of the process of metastasis and tumor invasion is required before proteases can be used as therapeutic targets for blocking the spread of cancer.

Relationship between Candida albicans producing proteinase (CAPP) and its environmental pH--comparison with a case of trichophyton mentagrophytes

Candida albicans produced a karatinolytic proteinase (KPase) or C. albicans producing proteinase (CAPP), a proposed new term for this enzyme, and Trichophyton mentagrophytes also produced KPase when cultivated in liquid medium containing human stratum corneum (HSC) as the nitrogen source, but were unable to do so when cultivated in sabouraud dextrose broth. Purified KPase from the culture supernatants of C. albicans had a molecular weight of 42,000 and an optimum pH at 4.0. The KPase was found to belong to the carboxyl proteinases group and its activity was strongly inhibited by pepstatin. Both fungi were able to grow by secreting KPase which digested HSC for nutrients. KPase from both fungi had high activity in each optimum pH, such as weakly acidic pH on C. albicans and neutral pH on T. mentagrophytes to adapt their surrounding environment by changing the environmental pH into their own optimum pH.