Evidence for the binding of a biologically active interleukin-2 to human alpha 2-macroglobulin

Human alpha 2-macroglobulin (alpha 2M), which irreversibly entraps proteinases through a drastic conformational change, has also been reported to bind various cytokines. The meaning of cytokine binding to native and/or transformed alpha 2M molecules is, however, not understood. In an attempt to eluc...

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Bibliographic Details
Published in:The Journal of biological chemistry 1995-04, Vol.270 (15), p.8381-8384
Main Authors: Legrès, L G, Pochon, F, Barray, M, Gay, F, Chouaib, S, Delain, E
Format: Article
Language:English
Subjects:
alpha-Macroglobulins - chemistry
alpha-Macroglobulins - metabolism
Cells, Cultured
Electrophoresis, Polyacrylamide Gel
Humans
Hydrolysis
Interleukin-2 - metabolism
Protein Binding
Protein Conformation
Recombinant Proteins - metabolism
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Summary:Human alpha 2-macroglobulin (alpha 2M), which irreversibly entraps proteinases through a drastic conformational change, has also been reported to bind various cytokines. The meaning of cytokine binding to native and/or transformed alpha 2M molecules is, however, not understood. In an attempt to elucidate this question, we have studied the interaction of radioiodinated recombinant human interleukin-2 (125I-rhIL-2) with native and chymotrypsin (alpha 2M-C)- or methylamine-transformed (alpha 2M-MA) alpha 2M. Our results show that native and alpha 2M-MA are able to bind 125I-rhIL-2, with binding occurring only with the latter in a covalent manner, whereas the labeled cytokine is proteolyzed when incubated with alpha 2M-entrapped chymotrypsin. The degradation of uncomplexed 125I-rhIL-2 has also been observed in the presence of trypsin, whereas 125I-rhIL-2 bound to alpha 2M-MA is protected. Moreover, the proliferative activity of this cytokine on responsive cells is still maintained either with native alpha 2M- or alpha 2M-MA-complexed rhIL-2 in comparison with that observed with the cytokine alone. Our results, which lead us to consider alpha 2M molecules as IL-2-binding proteins, emphasize the possible role of these molecules as immune response regulators.
ISSN:0021-9258