ULTRASTRUCTURAL STUDIES OF COMPLEMENT-MEDIATED CELL-DEATH - A BIOLOGICAL REACTION MODEL TO PLASMA-MEMBRANE INJURY

Complement-mediated nucleated cell death has been shown to be independ ent of colloid-osmotic swelling. In contrast, other factors (e.g. Ca2 influx) are of importance in the induction of cell death. In this com munication, the sequential morphological features of complement-mediat ed cell injury have been studied by electron microscopy and compared w ith biochemical data (ATP content and LDH release). It was observed th at immediately after C5b-8 lesion formation, although the overall cell morphology is well preserved, the mi tochondria display an ''ultracon densed'' appearance. Upon addition of C9, the mitochondria remain init ially condensed, but swell progressively with final formation of flocc ulent densities. The nuclei become progressively edematous, with concu rrent disappearance of heterochromatin. The nucleoli lose their associ ated chromatin and display segregation of their components with format ion of markedly electron-dense filamentous deposits. The nuclear envel ope remains initially intact, but subsequently progressive dilatation of the associated perinuclear RER cisterna and distention of the nucle ar pores associated with leakage of chromatin into the cytoplasm are s een. The larger cell organelles (including mitochondria, ER, Golgi app aratus, etc.) become clustered around the nucleus, concurrently with m arked edema of the outer cytoplasm and bleb formation. The RER cistern ae become dilated, whereas the Golgi complex disappears. Relatively ea rly on the plasma membrane shows breaks in continuity. The pattern of these changes - potentially related to Ca2+ influx, ATP efflux and ove rall metabolic depletion - corresponds to the previously described mod el of cell reaction to injury, confirming the dynamic nature of the pr ocess. The morphology of cell death in this model shares some features , e.g., the nucleolar changes, with ''apoptosis'' (programmed cell dea th). However, the overall pattern appears to correspond more to ''necr osis,'' characterized by loss of volume control and mitochondrial abno rmalities.