Mannose binding protein (MBP) is a calcium-dependent C-type lectin sec
reted by the liver which seems to be an important component of innate
or natural immunity. We have investigated the effects of Candida albic
ans and thioglycolate injection into transgenic mice bearing the human
MBP gene, The transgenes contained a 15 kb fragment of the MBP gene w
hich included the complete coding sequence, Northern blot hybridizatio
n showed human MBP mRNA transcripts in the liver of two transgenic lin
es with low and high copy number respectively. Western blot analysis s
howed the presence in serum of human MBP which associated into the hig
her multimeric forms which are capable of activating complement. Enzym
e-linked immunosorbent assays (ELISA) showed that serum human MBP conc
entrations in the transgenes (1.90 +/- 0.16 mg/l, mean +/- SEM) were a
bout twice as high as the levels in man, The serum concentration of MB
P A, which is the mouse homologue of MBP, (13.9 +/- 0.45 mg/l) was abo
ut seven times that of human MBP, Intravenous injection of Candida alb
icans 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 MB
P 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 bo
th transgenic lines. These data indicate that the human MBP gene fragm
ent in the transgene did not include the regulatory elements of the ge
ne. Total haemolytic complement activity and C3 concentrations also fe
ll. immediately after Candida and thioglycolate injection while the co
ncentrations of mannose specific immunoglobulin G (IgG) and immunoglob
ulin M (IgM) did not fall. The data indicate that mannose binding prot
ein plays an important role in the initial stages of defence against i
nfection which, in this model, is quantitatively greater than that of
mannose-specific IgG and IgM antibodies. Mannose binding protein is pr
obably most important in defense of previously unexposed and non-immun
e hosts.