Modulation of functional properties of galectin-3 by monoclonal antibodies binding to the non-lectin domains

Fu-Tong Liu, Daniel K. Hsu, Riaz I. Zuberi, Paul N. Hill, Amir Shenhav, Ichiro Kuwabara, Swey Shen Chen

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Abstract

Galectin-3 is a member of a newly defined family of animal lectins, which is composed of three domains: a small amino-terminal domain, a domain containing repeating elements, and a carboxyl-terminal domain containing the carbohydrate-recognition site. Various functions have been described or proposed for this lectin, and it appears that galectin-3 has diverse roles. Murine monoclonal antibodies (MAbs) have been generated from mice hyperimmunized with recombinant human galectin-3 or galectin-3C (the carboxyl-terminal domain), and seven MAbs have been characterized in detail. All MAbs generated against the intact galectin-3 recognize the amino- terminal region of the molecule, as demonstrated by ELISA and immunoblotting using recombinant galectin-3C and galectin-3NR, which contains the amino- terminal domain and all the repeating elements. Their epitopes were all found to be within the first 45 amino acids of galectin-3, as determined by using galectin-3 mutants with a truncated amino-terminal region. However, these MAbs were found to profoundly modulate the lectin activities of galectin-3. The MAb B2C10 inhibited (i) the binding of 125I-labeled galectin-3 to IgE coated on microtiter plates; (ii) the galectin-3's hemagglutination activity; and (iii) galectin-3-induced superoxide production by human neutrophils. Other MAbs, especially A3A12, caused marked potentiation of these activities. The results support our model that the lectin function of galectin-3 is influenced by protein homodimerization resulting from self-association of the amino-terminal region of the molecule. The potentiating activities of some MAbs are probably due to facilitation of dimerization of galectin-3, and the inhibitory activity of MAb B2C10 is probably the result of its disruption of the self-association process.

Original languageEnglish (US)
Pages (from-to)6073-6079
Number of pages7
JournalBiochemistry
Volume35
Issue number19
DOIs
StatePublished - May 14 1996

Fingerprint

Galectin 3
Monoclonal Antibodies
Modulation
Galectins
Lectins
Association reactions
Molecules
Dimerization
Hemagglutination
Immunoblotting
Superoxides
Immunoglobulin E
Epitopes
Neutrophils
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Biochemistry

Cite this

Liu, F-T., Hsu, D. K., Zuberi, R. I., Hill, P. N., Shenhav, A., Kuwabara, I., & Chen, S. S. (1996). Modulation of functional properties of galectin-3 by monoclonal antibodies binding to the non-lectin domains. Biochemistry, 35(19), 6073-6079. https://doi.org/10.1021/bi952716q

Modulation of functional properties of galectin-3 by monoclonal antibodies binding to the non-lectin domains. / Liu, Fu-Tong; Hsu, Daniel K.; Zuberi, Riaz I.; Hill, Paul N.; Shenhav, Amir; Kuwabara, Ichiro; Chen, Swey Shen.

In: Biochemistry, Vol. 35, No. 19, 14.05.1996, p. 6073-6079.

Research output: Contribution to journalArticle

Liu, F-T, Hsu, DK, Zuberi, RI, Hill, PN, Shenhav, A, Kuwabara, I & Chen, SS 1996, 'Modulation of functional properties of galectin-3 by monoclonal antibodies binding to the non-lectin domains', Biochemistry, vol. 35, no. 19, pp. 6073-6079. https://doi.org/10.1021/bi952716q
Liu, Fu-Tong ; Hsu, Daniel K. ; Zuberi, Riaz I. ; Hill, Paul N. ; Shenhav, Amir ; Kuwabara, Ichiro ; Chen, Swey Shen. / Modulation of functional properties of galectin-3 by monoclonal antibodies binding to the non-lectin domains. In: Biochemistry. 1996 ; Vol. 35, No. 19. pp. 6073-6079.
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