We have previously reported that isoproterenol induces type 2 salivary cystatin in both submandibular glands and kidney tubule cells of rats but not in any other organs examined. In the present study, we investigated whether this salivary protein is induced in other conditions that show kidney tubule injury. Immunocytochemistry, using a monospecific antiserum to this cystatin, revealed specific staining within the proximal tubule epithelium of the cortex as well as in the inner and outer stripe of the medulla of immunologically and chemically injured rats. Cystatin could not be detected in kidneys from healthy rats by means of immunocytochemistry. Weak staining was found in 3/3 kidneys of rats treated with turpentine and in 5/5 animals treated with potassium dichromate. In rats treated with puromycin, cystatin could not be demonstrated in 5/5 animals having proteinuria of less than 100 mg/24 h; however, moderate staining was observed in 4/5 puromycin-treated rats having proteinuria greater than 100 mg/24 h. In Heymann nephritis, cystatin was present in 7/31 kidneys with proteinuria lasting 6 to 15 weeks and in none (0/ 7) with proteinuria of shorter duration. Strong staining was also observed in 10/10 kidneys from rats with moderate-to-severe chronic serum sickness. This study shows that elaboration of type 2 cystatin in rats is not limited to salivary glands and, with our previous study, suggests that induction of this cysteine proteinase inhibitor may represent a local response to generalized tissue injury in both submandibular and renal tissues. These findings further demonstrate that induction of cystatin in salivary glands is not unique to these glands and suggest that induction of this cysteine proteinase inhibitor may represent a local response to tissue injury caused by diverse mechanisms.
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