The requirement for polymorphonuclear leukocytes in the late asthmatic response and heightened airways reactivity in an animal model

Abstract

The antigen-induced late asthmatic response (LAR) and subsequent heightened airways reactivity after this response have been associated with increased airways inflammation. Employing an animal model of the LAR in rabbits previously developed in our laboratory, 3 phases of experiments were performed to investigate the role of polymorphonuclear leukocytes (PML) in the LAR and heightened reactivity. In all 3 phases, airways reactivity to histamine and bronchoalveolar lavage analysis were performed 3 days before and 3 days after bronchial challenge with ragweed extract. In Phase 1, 2 groups of rabbits receiving nitrogen mustard were studied: an immune group received immune serum containing antiragweed IgE, and a control group received nonimmune serum. In Phase II, nitrogen mustard was administered to immune rabbits during aortic occlusion to allow the lungs to be exposed to nitrogen mustard while limiting exposure of the bone marrow to this drug, preventing depletion of PML. In Phase III, both an immune and a nonimmune group of rabbits received nitrogen mustard as in Phase I; however, prior to antigen challenge, they were repleted with a neutrophil-rich population of PML. In all experiments, no group of control (nonimmune) rabbits, whether depleted or repleted of PML, developed an immediate asthmatic response (IAR) or a LAR. In addition, no significant increases in lavage cells or airways reactivity occurred after ragweed challenge. In contrast, those animals receiving immune serum and nitrogen mustard developed an IAR; however, no LAR occurred, and no significant change in airways reactivity was observed. Rabbits receiving immune serum and nitrogen mustard with aortic occlusion developed an IAR and LAR, and airways reactivity increased.(ABSTRACT TRUNCATED AT 250 WORDS)