Effect of alpha4-integrin blockade on CD4+ cell-driven late airway responses in the rat.
The blockade of alpha4 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 alpha4-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 alpha4-integrin blockade may involve interference with CD4+ cell activation and IL-5 expression.
Ramos-Barbón
D
D
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Suzuki
M
M
Taha
R
R
Molet
S
S
Issekutz
T B
TB
Hamid
Q
Q
Martin
J G
JG
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D039441:Integrin alpha4; D007371:Interferon-gamma / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D007958:Leukocyte Count; D008168:Lung / Q000502:physiology*; D008297:Male; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011914:Rats, Inbred BN
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015848:Interleukin-5; D012333:RNA, Messenger; D039441:Integrin alpha4; D007371:Interferon-gamma