Vol. 293, Issue 2, 410-416, May 2000

Role of Cysteinyl Leukotrienes in CD4⁺ T Cell-Driven Late Allergic Airway Responses¹

Masayuki Hojo, Masaru Suzuki, Karim Maghni², Qutayba Hamid, William S. Powell and James G. Martin

Meakins-Christie Laboratories, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada

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 × 10⁶ cells) 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.