Effect of immunotherapy on the production of eosinophil adhesion-inducing activity from mononuclear cells in house-dust-mite-sensitive bronchial asthma.
An initial step of eosinophil (EOS) accumulation in the sites of allergic inflammation is the adhesion to endothelial cells. There is increasing evidence that immunotherapy (IT) modulates the production of cytokines from mononuclear cells and hence attenuates allergic inflammation. To examine whether IT modifies the production of factor(s) which induce EOS adhesion, peripheral blood mononuclear cells (PBMC) from house-dust-mite-sensitive asthmatics treated with or without IT were cultured for 96 h in the presence or absence of 1/microg/ml Dermatophagoides farinae antigen. EOS were isolated from the peripheral blood of healthy subjects. EOS adhesion-inducing activity (EAIA) in the PBMC culture supernatants was examined by the ability to modify EOS adhesion to paraformaldehyde-fixed human umbilical vein endothelial cells (HUVEC) which were stimulated with IL-4 plus TNF-alpha. In asthmatics without IT, the addition of D. farinae antigen significantly promoted the production of EAIA from PBMC (EOS adhesion: 22.4+/-13.1% by medium control vs. 30.5+/-18.9% by D. farinae, n=10, p=0.023). This enhancing effect was blocked by an anti-beta2-integrin antibody. In contrast, the addition of D. farinae did not modulate EAIA production from PBMC in asthmatics treated with IT (23.1+/-10.3% vs. 21.5+/-12.3%, n=10, p=NS). These results suggest that IT induces the inhibition of antigen-dependent production of EAIA from PBMC. This may contribute to the inhibitory effect of IT on eosinophil recruitment in allergic inflammation.
Pulmonary Division, Second Department of Internal Medicine, Saitama Medical School, Saitama, Japan.
M
M
Nagata
K
K
Tabe
J
J
Hong Choo
Y
Y
Sakamoto
H
H
Matsuo
D000818:Animals; D001249:Asthma / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D002448:Cell Adhesion; D002478:Cells, Cultured; D003888:Desensitization, Immunologic; D004391:Dust / Q000009:adverse effects; D004730:Endothelium, Vascular / Q000166:cytology; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008925:Mites / Q000276:immunology
D004391:Dust