Inhibitory effect of heparin-derived oligosaccharides on secretion of interleukin-4 and interleukin-5 from human peripheral blood T lymphocytes.
OBJECTIVE
To investigate the inhibitory effect of heparin-derived oligosaccharides (Oligs) on secretion of interleukin-4 (IL-4) and interleukin-5 (IL-5) from human peripheral blood T lymphocytes (PBTLs).


METHODS
Oligs were prepared by three different heparin depolymerization methods and separated by gel filtration chromatography. PBTLs from ten adult patients with allergic eosinophilic gastroenteritis were treated with phytahematoagglutinin (PHA) and Oligs. The supernatants from the cell culture of PBTLs were harvested and subjected to the determination of IL-4 and IL-5 contents by ELISA method.


RESULTS
At the concentration of 5 microg/mL, Oligs with different Mr had different effects on the secretion of IL-4 and IL-5. The tetrasaccharide with Mr of 1,142, produced by depolymerizing heparin with hydrogen peroxide, had the strongest inhibitory effect on the secretion of IL-4. It decreased the IL-4 content from 375.6+/-39.2 ng/L (PHA group) to 12.5+/-5.7 ng/L (P<0.01). The hexasaccharide with Mr of 1,806, produced by depolymerizing heparin with beta-elimination method, had the strongest inhibitory effect on the secretion of IL-5. It decreased the IL-5 content from 289.2+/-33.4 ng/L (PHA group) to 22.0+/-5.2 ng/L (P<0.01).


CONCLUSIONS
The inhibitory activity of Oligs on the secretion of IL-4 and IL-5 from human PBTLs closely depends on their molecular structure, and there may be an essential structure to act as an inhibitor. The most effective inhibitors of IL-4 and IL-5 secretion are tetrasaccharides and hexasaccharides, respectively.
Ji
Sheng-Li
SL
Key Laboratory of Marine Drugs, Marine Drug and Food Institute, Ocean University of China, Qingdao 266003, Shandong Province, China. shengliji@sdu.edu.cn
Cui
Hui-Fei
HF
Shi
Feng
F
Chi
Yan-Qing
YQ
Cao
Ji-Chao
JC
Geng
Mei-Yu
MY
Guan
Hua-Shi
HS
D000328:Adult; D002478:Cells, Cultured; D002850:Chromatography, Gel; D004804:Eosinophils / Q000276:immunology; D005759:Gastroenteritis / Q000276:immunology*; D006493:Heparin / Q000737:chemistry; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D015847:Interleukin-4 / Q000378:metabolism*; D015848:Interleukin-5 / Q000378:metabolism*; D008970:Molecular Weight; D009844:Oligosaccharides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D015848:Interleukin-5; D009844:Oligosaccharides; D015847:Interleukin-4; D006493:Heparin