Abstract

Cysteinyl leukotrienes (cys LTs) play an important role in late responses to allergen challenge of actively sensitized rats. The aim of this study was to determine whether T cell-dependent late airway responses (LARs) also are mediated by cys LTs. To do this we tested the effects of the selective and potent LTD₄ antagonist pranlukast on airway responses to ovalbumin (OVA) challenge of naive recipients of CD4⁺ T cells isolated from the cervical lymph nodes of OVA-sensitized donor rats. CD4⁺ T cells (5 million) were purified by immunomagnetic separation and administered i.p. 2 days before OVA challenge. The pulmonary resistance was measured for 8 h after challenge and bronchoalveolar lavage (BAL) was performed for analysis of leukocytes and major basic protein-positive cells. The LAR, determined as the area under the curve of pulmonary resistance against time from 3 to 8 h after challenge, was 8.9 ± 1.79 cm H₂O/ml/s × min after OVA compared with 2.8 ± 0.50 cm H₂O/ml/s × min (P < .01) after OVA and pranlukast treatment. The total cell count in BAL was not significantly greater in the OVA challenged group (3.55 ± 0.41 × 10⁶cells) compared with the OVA- and pranlukast-treated group (2.65 ± 0.45 × 10⁶ cells). However, lymphocytes and eosinophils were reduced in numbers by pranlukast. Interleukin-5 mRNA-positive cells were diminished by 50% in pranlukast-treated animals. In conclusion, pranlukast inhibits LAR, BAL eosinophilia, and Interleukin-5 expression in rats with adoptively transferred LAR, indicating an important role for cys LTs in these T cell-driven responses.