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Am. J. Respir. Crit. Care Med., Volume 163, Number 1, January 2001, 101-108

Effect of alpha 4-Integrin Blockade on CD4+ Cell-driven Late Airway Responses in the Rat

DAVID RAMOS-BARBÓN, MASARU SUZUKI, RAME TAHA, SOPHIE MOLET, THOMAS B. ISSEKUTZ, QUTAYBA HAMID, and JAMES G. MARTIN

Meakins-Christie Laboratories, McGill University, Montreal, Quebec; and Dalhousie University, Halifax, Nova Scotia, Canada

The blockade of alpha 4 integrins with a monoclonal antibody (TA-2) decreases late airway responses (LR) in ovalbumin (OVA)-sensitized and challenged rats. In this study, we used a model of CD4+ cell-driven LR to test the hypothesis that alpha 4-integrin blockade involves interference with T-cell activation in the inhibition of LR. Purified CD4+ cells from OVA-sensitized rats were transferred to unsensitized recipients, which received either TA-2 or a control antibody (cAb), and were OVA-challenged. A sham-challenged group was also studied. LR, calculated from pulmonary resistance after challenge, were reduced in the TA-2 group compared with the cAb group (p = 0.015). Total cell counts, macrophages, neutrophils, and lymphocytes in bronchoalveolar lavage (BAL), and CD3+ cells in airway sections, were unaffected. The cAb group had higher numbers of cells expressing interleukin-5 (IL-5) mRNA (55.2 ± 3.39 cells/1,000, mean ± SEM) and major basic protein (MBP) (6.2 ± 0.4/100 cells) in bronchoalveolar lavage (BAL), than the TA-2 group (25.37 ± 2.41 IL-5+ and 2.7 ± 0.2 MBP+) and the sham group (12.37 ± 0.96 IL-5+, 1.7 ± 0.1 MBP+). Interferon gamma (IFN-gamma ) mRNA+ cells were downregulated in both OVA-challenged groups, compared with the sham group. Our results suggest that the attenuation of LR and eosinophilia by alpha 4-integrin blockade may involve interference with CD4+ cell activation and IL-5 expression.




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