[CD86 expression on alveolar macrophages and effects of anti-CD86 monoclonal antibody on the production of inflammatory cytokines in dust-mite allergic asthma patients].
OBJECTIVE
To investigate the CD(86) molecule expression on alveolar macrophages (AMs) before and after AM activation with dust-mite allergen and effects of anti-CD(86) monoclonal antibody on the production of inflammatory cytokines produced by cultured CD(34)(+) T cells, and to explore the pathogenesis of anti-CD(86) monoclonal antibody on inhibiting asthmatic inflammation.


METHODS
AMs and CD(34)(+) T cells were isolated from bronchoalveolar lavage fluid (BALF) and from peripheral blood derived from 10 asthma patients allergic to house dust-mite dermatophagoides pteronyssinus. AMs were stimulated and activated by house dust-mite allergen and co-cultured with CD(34)(+) T cells. The co-cultured cells were divided into anti-CD(86) monoclonal antibody intervention group and CD(86) expression group with which the control groups were set up. The anti-CD(86) antibody was added to 0.1 mg/L and 1.0 mg/L in the experiment group and no antibody was added in the control group. The supernatants were harvested after 72 hour co-culture. The concentration of interferon-gamma (INF-gamma), interleukin-4 (IL-4) and IL-5 were determined by enzyme linked immunosorbent assay (ELISA). CD(86) expression group was divided into experiment and control groups, and house dust-mite allergen was added to the experiment group but no allergen was added in the control group. The cells of the two groups were harvested after 24 hour co-culture. The CD(86) molecule expression on the AMs was detected by flow cytometry.


RESULTS
After activated by house dust-mite allergen, the average fluorescence density of CD(86) on AM in the experiment group [(50 +/- 9)%] was significantly higher than that in the control group [(23 +/- 5)%, P < 0.01]. The production of IL-4 and IL-5 was (135 +/- 19) ng/L, and (104 +/- 21) ng/L in the low-dose group respectively; (90 +/- 17) ng/L and (68 +/- 14) ng/L in the high-dose group; (187 +/- 24) ng/L and (161 +/- 23) ng/L in the control group; the differences among groups were significant (P < 0.01). The production of IFN-gamma was (193 +/- 39) ng/L in the low-dose group and (201 +/- 47) ng/L in the high-dose group respectively, and there was no significant difference between the two groups (P > 0.05).


CONCLUSIONS
AMs may effectively present allergen to T cells in allergic asthma patients. Anti-CD(86) monoclonal antibody can inhibit the production of IL-4 and IL-5 by blocking the co-stimulatory signal of CD(34)(+) T cells. These data suggest that anti-CD(86) monoclonal antibody may hold therapeutic potentials in asthma by inhibiting airway inflammation.
Chen
Ping
P
Department of Respiratory Diseases, General Hospital of Shenyang Military Region, Shenyang 110015, China.
Wu
Wei
W
Ma
Zhuang
Z
Gao
Yan
Y
Zhao
Hai-tao
HT
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D051940:B7-2 Antigen / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D016676:Macrophages, Alveolar / Q000166:cytology / Q000276:immunology*; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D051940:B7-2 Antigen; D015848:Interleukin-5; D015847:Interleukin-4; D007371:Interferon-gamma