MOSQUITO TRANSFERRIN, AN ACUTE-PHASE PROTEIN THAT IS UP-REGULATED UPON INFECTION

When treated with heat-killed bacterial cells, mosquito cells in cultu re respond by up-regulating several proteins, Among these is a 66-kDa protein (p66) that is secreted from cells derived from both Aedes aegy pti and Aedes albopictus. p66 was degraded by proteolysis and gave a v irtually identical pattern of peptide products for each mosquito speci es, The sequence of one peptide (31 amino acids) was determined and fo und to have similarity to insect transferrins, By using conserved regi ons of insect transferrin sequences, degenerate oligonucleotide PCR pr imers were designed and used to isolate a cDNA clone encoding an A. ae gypti transferrin. The encoded protein contained a signal sequence tha t, when cleaved, would yield a mature protein of 68 kDa. It contained the 31-amino acid peptide, and the 3' end exactly matched a cDNA encod ing a polypeptide that is up-regulated when A. aegypti encapsulates fi larial worms [Beerntsen, B. T., Severson, D. W. & Christensen, B. M. ( 1994) Exp. Parasitol. 79, 312-321], This transferrin, like those of tw o other insect species, has conserved iron-binding residues in the N-t erminal lobe but not in the C-terminal lobe, which also has large dele tions in the polypeptide chain, compared with transferrins with functi onal C-terminal lobes, The hypothesis is developed that this transferr in plays a role similar to vertebrate lactoferrin in sequestering iron from invading organisms and that degradation of the structure of the C-terminal lobe might be a mechanism for evading pathogens that elabor ate transferrin receptors to tap sequestered iron.