Apoptosis in Lymphadenitis and Malignant Lymphoma.

Abstract

The concept of apoptosis was originally proposed by Kerr et al. in 1972. Its morphological features involve nuclear and cytoplasmic condensation, apoptotic body and rapid uptake by phagocytes. This form of cell death effects single cells with living tissue without disruption of either architecture or function. The process of apoptosis avoids both the release of intracellular contents into the tissue and the resulting inflammation which characterizes necrosis. Apoptotic phenomenon was recently confirmed by biochemical and immunohistological techniques such as electrophoresis and the TUNEL method for DNA fragmentation.We used 36 cases of lymphadenitis including necrotizing lymphadenitis (24 cases), abscess forming lymphadenitis (3 cases), tuberculous lymphadesitis (3 cases), tularemia (3 cases), non-specific lymphadenitis (3 cases) and 140 cases of non-Hodgkin's lymphomas (NHLs).In necrotizing lymphadenitis, apoptotic cells which correspond to CD 4+ lymphocytes are localized at the necrobiotic focus (7.9%). Fas antigen is observed in blastoid cells (CD 8+) and Fas-ligand is present in macrophages. In addition, we detected human herpesvirus 6 (HHV 6) particles, antigens and genomes within phagocytized cells. These findings suggest that apoptosis in necrotizing lymphadenitis may be induced by virus or non-bacterial agents rather than the Fas/Fas-ligand system.In the high-grade group of NHLs, c-myc and p-53 oncogens are highly expressed but bcl-2 protein is lower. C-myc positive NHLs are significantly rich in TUNEL-positive (apoptotic) cells. In addition, it is known that bcl-2 protein tends to impede apoptosis mediated by c-myc oncogen.Our data show that the coexpression of c-myc and p-53 oncogens may induce apoptosis rather than Fas and bcl-2 oncogens because of a lower inhibitory effect of bcl-2 protein in the high-grade group.Apoptosis is an important cell regulator in tissues under both physiological and pathological conditions. The induction mechanism of apoptosis is different among reactive diseases and malignancy and it requires intimate studies from the standpoint of molecular biological aspects.