FORMATION OF TIGHT JUNCTIONS AND DESMOSOMES PROTECTS MDCK CELLS AGAINST HYPERTHERMIC KILLING

Cell density is known to modify the survival of mammalian cells exposed to elevated temperatures. We have examined the role that cell-cell contact plays in this phenomenon. The formation of cell-cell contact is carried out by cells' junctional complex, i.e., tight junctions, desmosomes, and gap junctions. Lack of formation of tight junctions and desmosomes, or their opening, could interfere with the functions and structures of cell membrane. Membrane damage is at least partially responsible for cell death at elevated temperatures. MDCK cells with high density plated in low calcium medium form confluent monolayers devoid of the formation of tight junctions and desmosomes but quickly assemble them after Ca2+ restoration. We used MDCK cells and the calcium switch technique to investigate effects of cell-cell contact and, independently, of cell density on hyperthermic cell killing. We found that MDCK cells that formed tight junctions and desmosomes were more resistant to hyperthermic treatment than those that did not. Blocking the formation pathway of tight junctions made cells sensitive to heat. Cells growing at lowdensity showed almost the same survival as did cells at high density in the absence of the formation of tight junctions and desmosomes. The results suggest that the formation of tight junctions and desmosomes play a more important role in determining hyperthermic response than does density per se. The formation of tight junctions and desmosomes appears to protect cells modestly against hyperthermic killing. (C) 1994 Wiley-Liss, Inc.