Cytoplasmic vacuolation, adaptation and cell death: A view on new perspectives and features

Abstract

The review focuses on a widely-observed morphological phenomenon, a unique class of cytoplasmic vacuolation, found in cultured (mammalian) cells. This vacuolation is quite distinct from autophagosomal and heterophagosomal, i.e. excessive lysosomal vacuolation, and occurs in most cell types spontaneously or via a wide range of inductive stimuli. Apart from vacuolation arising artefactually (usually due to poor fixation), spontaneous vacuolation occurs in individual or small clusters of cultured cells without apparent change in their local environment, while neighbouring cells remain completely unaffected. Since spontaneous vacuolation is unpredictable, the process of vacuolation--or 'vacuolisation'--('Vacuolation' is the state of being with vacuoles; 'vacuolisation' therefore implies the process of becoming vacuolated. However, only the quicker term vacuolation will be used throughout this review to refer to the process of vacuole development.) induced experimentally, and hence relatively reproducibly by a range of substances and disturbances, offers an experimental approach which should give further insight into its physiology and pathophysiology. Unfortunately, our knowledge here remains woefully inadequate compared with the purely morphological aspects of the phenomenon. Vacuolation following disturbances could have an underlying common mechanism; however, a review of the literature suggests that this is not the case, and that it occurs via several different pathways, involving many different cell organelles and structures. All cells appear to retain the capacity to vacuolate for some physiological purpose, and it can be a permanent feature in many cell types, particularly 'lower' organisms and plants. Vacuolation in cells is generally seen as an adaptive physiological response, presumably for 'damage limitation', but very little is known about the intracellular homeostatic mechanisms which operate to restore the status quo. Where damage limitation fails, cells usually die quickly, but no clear evidence has been found that this is in any way 'programmed'. It is argued that the demise which occurs via the vacuolation route may, in fact, be a distinct form of cell death which is difficult to fit into the conventional lytic and apoptotic modes.

Effects of various pollutant mixtures on immune responses of the blue mussel (Mytilus edulis) collected at a salinity gradient in Danish coastal waters

“…The correlation of high values of THC with occurrences of morphological changes, particularly vacuolation, may suggest a compensation of reduced cell viability. In agreement with Henics and Wheatley (1999), we therefore suggest that vacuolation in mussel haemocytes may be implemented as a marker for decreased cell viability.…”

“…Vacuolation has been described as a potential marker for environmental stress in mussel tissues, such as the epithelial (Auffret, 1988) and digestive cells (Thompson et al, 1978), though descriptions of vacuolation events in haemocytes are lacking. Henics and Wheatley (1999) provided a review about the occurrence and implications of cytoplasmic vacuolation in cultured mammalian cells, suggesting that this abnormality primarily reflects an adaptative, survival response to a wide range of environmental factors, which is reversible but could lead to a particular and distinctive form of cell death (rather than apoptosis). Additionally, McCormick-Ray and Howard (1991) excluded haemocytes with vacuoles in a morphology and mobility study as those may have been dead or dying cells.…”

Upregulated autophagy protects cardiomyocytes from oxidative stress-induced toxicity

“…5C), a phenomenon often observed with injury, toxicity and cell death. 40 Treatment with rapamycin drastically decreased the appearance of such vacuoles (Fig. 5C).…”

The autophagosomal–lysosomal compartment in programmed cell death

“…77 However, apoptotic bodies (ABs) can be discriminated from autophagic vacuoles (AVs) based upon the chromatin residues present in ABs, but usually not in AVs; electronmicroscopy and/or specific stains to visualise DNA revealed to be most helpful tools as reviewed previously. 75 Finally, in cultured cells cytoplasmic vacuolisation is widely observed, but this type of vacuolisation is considered to be distinct from that consequently to autophagy (for review: 78 ). Taken together, these phenomena should be taken into account and appropriate techniques should be used to verify gross morphological observations.…”