TY - JOUR T1 - Role of Cysteinyl Leukotrienes in CD4<sup>+</sup> T Cell-Driven Late Allergic Airway Responses JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 410 LP - 416 VL - 293 IS - 2 AU - Masayuki Hojo AU - Masaru Suzuki AU - Karim Maghni AU - Qutayba Hamid AU - William S. Powell AU - James G. Martin Y1 - 2000/05/01 UR - http://jpet.aspetjournals.org/content/293/2/410.abstract N2 - 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 &lt; .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. The American Society for Pharmacology and Experimental Therapeutics ER -