Mannose binding protein is involved in first-line host defence: Evidence from transgenic mice

P. Tabona, A. Mellor, J. A. Summerfield

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Mannose binding protein (MBP) is a calcium-dependent C-type lectin secreted by the liver which seems to be an important component of innate or natural immunity. We have investigated the effects of Candida albicans and thioglycolate injection into transgenic mice bearing the human MBP gene. The transgenes contained a 15kb fragment of the MBP gene which included the complete coding sequence. Northern blot hybridization showed human MBP mRNA transcripts in the liver of two transgenic lines with low and high copy number respectively. Western blot analysis showed the presence in serum of human MBP which associated into the higher multimeric forms which are capable of activating complement. Enzyme-linked immunosorbent assays (ELISA) showed that serum human MBP concentrations in the transgenes (1.90 ± 016 mg/l, mean ± SEM) were about twice as high as the levels in man. The serum concentration of MBP A, which is the mouse homologue of MBP, (13.9 ± 0 45 mg/l) was about seven times that of human MBP. Intravenous injection of Candida albicans caused the serum human MBP level to fall by more than 50% in the first hour and then slowly recover, but it did not return the initial value by 72 hr. Candida injection caused a 25% fall in serum mouse MBP A in the first hour which then rose to supranormal levels by 72 hr. Following Candida injection mouse MBP A mRNA concentrations increased over 72 hr in contrast to human MBP mRNA which remained constant in both transgenic lines. These data indicate that the human MBP gene fragment in the transgene did not include the regulatory elements of the gene. Total haemolytic complement activity and C3 concentrations also fell immediately after Candida and thioglycolate injection while the concentrations of mannose specific immunoglobulin G (IgG) and immunoglobulin M (IgM) did not fall. The data indicate that mannose binding protein plays an important role in the initial stages of defence against infection which, in this model, is quantitatively greater than that of mannose-specific IgG and IgM antibodies. Mannose binding protein is probably most important in defense of previously unexposed and non-immune hosts.

Original languageEnglish (US)
Pages (from-to)153-159
Number of pages7
JournalImmunology
Volume85
Issue number1
StatePublished - Jan 1 1995

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Mannose-Binding Lectin
Transgenic Mice
Transgenes
Candida
Thioglycolates
Serum
Injections
Mannose
Candida albicans
Innate Immunity
Messenger RNA
Immunoglobulin M
Immunoglobulin G
Complement Hemolytic Activity Assay
Genes
C-Type Lectins
Complement C3
Liver
Regulator Genes
Intravenous Injections

ASJC Scopus subject areas

  • Immunology

Cite this

Tabona, P., Mellor, A., & Summerfield, J. A. (1995). Mannose binding protein is involved in first-line host defence: Evidence from transgenic mice. Immunology, 85(1), 153-159.

Mannose binding protein is involved in first-line host defence : Evidence from transgenic mice. / Tabona, P.; Mellor, A.; Summerfield, J. A.

In: Immunology, Vol. 85, No. 1, 01.01.1995, p. 153-159.

Research output: Contribution to journalArticle

Tabona, P, Mellor, A & Summerfield, JA 1995, 'Mannose binding protein is involved in first-line host defence: Evidence from transgenic mice', Immunology, vol. 85, no. 1, pp. 153-159.
Tabona, P. ; Mellor, A. ; Summerfield, J. A. / Mannose binding protein is involved in first-line host defence : Evidence from transgenic mice. In: Immunology. 1995 ; Vol. 85, No. 1. pp. 153-159.
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