A guinea pig model to study effects of persistent intrabronchial antigenic stimulation and inflammation

Chronic antigenic stimulation and inflammation of the bronchial tree occurs in several diseases involving microbial airway colonization. We developed a guinea pig model to study the effects of persistent intrabronchial antigenic stimulation with keyhole limpet hemocyanin (KLH). Sepharose beads 200 to 300 micron in diameter conjugated with 300 micrograms KLH were injected via a tracheostomy catheter, causing them to lodge in the bronchial tree. When lung sections from these animals and animals given uncoupled sepharose beads were examined histologically, it became apparent that in this model the persistent antigenic stimulus is accompanied by local inflammation caused by an irritant effect of the beads. To determine how the intrabronchial antigen was distributed locally and systemically, 125I labeled KLH-coupled beads were administered. Radioactivity remained predominantly in the lung, where 13 +/- 5% of the administered dose was still detectable by Day 30. Autoradiographs of Day 30 lung sections demonstrated that the radioactivity was concentrated on the individual beads, indicating that it largely represented KLH persisting in the bronchial tree. Minute amounts of radioactivity were detected systemically and in the regional lymph nodes (LN). A radioimmune assay of serum collected on Day 1 demonstrated that some of the circulating radioactivity represented antigenic KLH. When anti-KLH antibody-forming cells (AFC) were measured in lung homogenate, regional LN, blood, and spleen cell preparations after KLH-coupled bead administration, they were initially detected only in the spleen. Significant concentrations appeared in the lung homogenate, regional LN, and spleen by Day 10 and thereafter through Day 20.(ABSTRACT TRUNCATED AT 250 WORDS)