GOBLET CELL DEGRANULATION AFTER ANTIGEN CHALLENGE IN SENSITIZED GUINEA-PIGS - ROLE OF NEUTROPHILS

Mucus hypersecretion is a common characteristic of asthma. Acute sever e asthma is often associated with neutrophilic infiltration into airwa ys. Neutrophils contain elastase, a potent secretagogue in airways. Th erefore, we hypothesized that instillation of ovalbumin in sensitized guinea pigs causes goblet cell secretion by releasing elastase from re cruited neutrophils. When we instilled ovalbumin into the trachea of o valbumin-sensitized guinea pigs, early recruitment of neutrophils iden tified by 3,3'-diaminobenzidine staining, and goblet cell degranulatio n measured with a semiautomatic computer-based imaging system occurred . The Leumedin NPC 15669 (a drug that inhibits leukocyte recruitment) and an antibody to intercellular adhesion molecule-1 (ICAM-1) both pre vented neutrophil recruitment and goblet cell degranulation, implicati ng leukocytes in the response. Using immunofluorescence we showed that the leukocytes recruited early after antigen challenge were CD-16-pos itive, implicating neutrophils. Pretreatment with the selective neutro phil elastase inhibitor ICI 200,355 also prevented ovalbumin-induced g oblet cell degranulation, implicating elastase. We conclude that ovalb umin-induced goblet cell degranulation is due to neutrophil recruitmen t and elastase release.