In vitro passive sensitization of the ureter as a basis for the study of noninfectious ureteral inflammation

To develop an in vitro model of passive sensitization for the ureter for the study of noninfectious ureteral inflammation.

Human ureteral tissues were obtained from excess segments of ureters from patients undergoing donor nephrectomy. Following excision, ureters were placed in physiologic salt solution (PSS) and passively sensitized by incubating with ragweed serum from allergic donor (1 ml. serum: 4 ml. PSS) for 20 hours at room temperature. Ureteral segments were incubated with PSS only and served as non-sensitized controls (n = 4). After sensitization, excess serum was removed by serial washing with PSS without serum. Ureteral strips were then suspended in vitro for determination of tissue contraction. Contractile responses and histamine release were measured. Tissues were then exposed to antigen. To investigate the role of inflammatory mediators in tissue contraction, 4 groups of 8 sensitized ureteral segments were incubated for 1 hour with the following substances: a H1 histamine receptor antagonist (pyrilamine), an inhibitor of prostaglandin synthesis (indomethacin), an inhibitor of leukotriene synthesis (A-64077), and a control substance (DMSO). Following incubation, the tissues were exposed to antigen, and contraction and histamine release were determined.

Sensitized ureteral segments (n = 8) responded to antigen with contraction (30% BaCl maximum; p <0.01) and histamine release (205/ng./gm. tissue) within the first 5 minutes of superfusion. Non-sensitized control segments (n = 4) did not respond. Both indomethacin and pyrilamine reduced (7-10% of BaCl maximum; p <0.05) the contractile response of sensitized ureter to antigen, whereas A-64077 did not. Analysis of the superfusate for histamine indicates that indomethacin reduced histamine release (150 ng./gm.) whereas A-64077 and pyrilamine did not (p <0.05).

We have demonstrated that ureteral segments can be passively sensitized and that subsequent antigen challenge stimulates contraction and histamine release. Our findings suggest that contraction of ureteral tissue and histamine release may be utilized as an inherent bioassay indicating the activity of inflammatory mediators. In addition, these results suggest that both prostaglandins and histamine, but apparently not leukotrienes, participate in the early inflammatory response to antigen challenge of the sensitized ureter.