Beta1 integrin-mediated adhesion between renal tubular cells after anoxic injury.

Abstract

beta 1 integrin-mediated adhesion between renal tubular cells after anoxic injury. This study examined the effect of sublethal injury, induced by ATP depletion (5 mM cyanide in the absence of dextrose), on the distribution and function of beta 1 integrins in primary cultures of mouse proximal tubular (MPT) cells. It was shown in this study that sublethal injury results in loss of focal contacts present in uninjured MPT cells, and that the beta 1 integrin molecule becomes redistributed to the apical membrane domain of sublethally injured cells. Polystyrene beads coated with Arg-Gly-Asp (RGD)-containing peptide adhere to the surface of sublethally injured MPT cells but not to control, dextrose-treated cells, indicating that the beta 1 integrins present on the apical surface of the cell remain functional. The presence of an excess of free RGD-containing peptide reduces binding of RGD-coated beads to sublethally injured MPT cells by approximately 50%. It was also demonstrated that adherence of MPT cells in suspension to cyanide-treated monolayers is increased more than 300% above adhesion to control, uninjured monolayers. This abnormal cell-cell adhesion is ameliorated by the presence of an excess of RGD-containing peptide and is reversed if cyanide-treated cells are allowed to recover for 1 h. It was concluded that the beta 1 integrin becomes expressed on the apical surface of MPT cells after sublethal injury. These apically expressed integrins remain functional and mediate aberrant adhesion between MPT cells.