Apoptosis is characterized by morphological features, among the most prominent are chromatin condensation, shrinking of cell and nucleus, and the fragmentation of the nucleus into membrane-enclosed bodies (karyorrhexis). After UV irradiation, we found in mouse cell line (BV-2) microglia an apoptotic phenotype in which, after chromatin condensation, the nucleus does not fragmentize, but shrinks due to production of vesicles from the nuclear envelope and release of chromatin into the cytoplasm [1]. DNA laddering revealed internucleosomal fragmentation already 1 h after irradiation, in contrast to the later onset of structural features of apoptosis (e.g. chromatin condensation). By conducting an immunogold labelling with anti-histone H3 for transmission electron microscopy, we found that histone H3 was not only located in the cytoplasm, but also at different areas of the plasma membrane region.

Recently, we were able to make similar observations in primary murine microglia. Primary apoptotic microglia also showed condensed chromatin in the nuclear periphery, a strongly dilated nuclear envelope with numerous vesicles in its immediate vicinity, and cytoplasmic chromatin, although the process of chromatin release from the nucleus is less pronounced than in BV-2 microglia.

Our study demonstrated that apoptotic microglia cells release chromatin into their cytoplasm and, presumably, accumulate histones in their plasma membrane. Since nuclear components are known to be potent immunoreactive agents, this mechanism could play a role in inflammatory processes.

[1] Zierler S, Klein B, Furtner T, Bresgen N, Lütz-Meindl U, Kerschbaum HH.

(2006) Ultraviolet irradiation-induced apoptosis does not trigger nuclear fragmentation but translocation of chromatin from nucleus into cytoplasm in the microglial cell-line, BV-2. Brain Res. 1121(1):12-21.