The pathogenesis of chronic inflammation and malignant transformation in the human upper airways: the role of beta-defensins, eNOS, cell proliferation and apoptosis.

The surrounding environment contains plenty of pathogens, which represent a danger of infection. The simplest way for the pathological microorganism to enter the organism is the upper airways. Inflammation of the upper airways is among the most common and frequent diseases. This category includes nasal polyposis and chronic tonsillitis. In many cases it is associated with disorders in relation to the immune response. An inflammatory infiltration of mononuclears, eosinophils, plasma and mast cells can be found in the histological structure of the polypous as well as tonsillar mucosa. One aim of this study was to determine the expression of beta-defensins and various proteins, with a possible potential role in relation to the rise and development of those changes. Another aim was to determine the relationship between the inflammatory and malignant processes in the tonsils. The samples of nasal polyps were obtained during clinically indicated endonasal surgery from patients diagnosed with nasal polyposis (n=50). The samples of tonsils were collected during surgery from patients suffering from chronic tonsillitis (n=11) or tonsillar carcinoma (n=17). Immunohistochemical procedures for the detection of human beta-defensin 1, 2, 3 (HBD-1, 2, 3), Ki- 67, endothelial nitric oxide synthase (eNOS) and cleaved caspase 3 were performed on cryostate and paraffin sections. It was proven that HBD are secreted in fairly large amounts in cases of chronic inflammation. Their secretion during the malignant transformation is limited. This is a very probable fact that plays a role in malignant transformation in tonsillar tissue. The crucial role in the development of chronic inflammation, and maybe that of malignant transformation, is played by eNOS and its product NO molecule. eNOS and the NO molecule are involved in cell cycle regulation, in the apoptotic processes and cell proliferation, as well as in the angiogenesis and vasculogenesis. Our result confirmed that eNOS is presented in the tissues of the upper airways in both chronic inflammation and carcinomatous processes. Ki-67 and cleaved caspase 3 were used as markers of cell proliferation and apoptosis.

Expression of endothelial and inducible nitric oxide synthase and caspase-3 in tonsillar cancer, chronic tonsillitis and healthy tonsils.

Neoangiogenesis and inhibition of apoptosis are two factors considered as major leading causes of tumorigenesis. NO, synthesized by NOS, plays an important role in tumour growth, dissemination and vascularization. Caspase-3 is an executive enzyme of apoptosis. The presented research work has been focused on the comparative evaluation of localization of the angiogenic and proapoptotic cytokines expressed in tonsillar diseases. The immunohistochemical reaction of eNOS, iNOS and caspase-3 in tonsillar cancer (N = 17), chronic tonsillitis (N = 11) and clinically healthy tonsils (N = 8) was detected. High eNOS occurrence in endothelial cells of highly vascularized regions in tonsillar cancer, variable eNOS expression in the vessels of lamina propria in chronic tonsillitis and high expression in the cytoplasm of endothelial cells of small veins in healthy tonsillar tissue was ascertained. Increased iNOS expression was found in cancer tissue in comparison with the healthy tonsils. Nevertheless, the highest expression of iNOS was found in chronic tonsillitis. Higher expression of caspase-3 was discovered in germinal centres of lymphoid follicles of the chronic tonsillitis tissue. However, the positivity in the interfollicular zone and surface squamous epithelium was weak only. Merely isolated caspase-3-positive cells were found in tonsillar cancer. Very low expression of caspase-3 was detected in the lymphatic follicles of the healthy tonsils. Research results showed high expression of eNOS in the carcinomatous tissue. The eNOS expression in chronic tonsillitis confirms its role in regulating the lymphocyte circulation. Low expression of caspase-3 in malignant epithelial cells of tonsillar cancer shows decreased capability of apoptosis compared to chronic tonsillitis tissue, where apoptosis seems to be rather frequent and concentrated in the germinal centres of lymphatic follicles. The differences in localization of eNOS and caspase-3 expression between benign and malignant processes may be a promising tool for precise morphological distinction of chronic inflammation and tumours.