No abstract

IFN-γ receptor-deficient (IFN-γR(-/-)) mice and control wild-type (WT) mice, with or without chloroquine (CQ) treatment, were infected intraperitoneally with Plasmodium yoelii 17XL (lethal) and P. yoelii 17XNL (nonlethal), and then mouse survival, parasitemia, and antibody production were investigated during the course of infection. Without CQ treatment, both IFN-γR(-/-) and WT mice were susceptible to infection showing 100 % mortality after infection with 1 × 10(5) P. yoelii 17XL-parasitized erythrocytes. The P. yoelii 17XL-infected WT mice could survive by CQ treatment at a dose of 20 mg/kg for 3 days from day 3 postinfection (pi). Malaria parasites in their bloodstream could not be detected in the surviving mice after day 13 pi. CQ treatment, however, could not rescue IFN-γR(-/-) mice infected with P. yoelii 17XL. Next, we examined the production of the parasite-specific antibodies in P. yoelii 17XL-infected, CQ-treated mice. Although the production of malaria-specific IgG1, IgG2a, IgG2b, and IgG3 antibodies was observed on days 14 and 28 pi in WT mouse sera, only IgG1 was detected on day 28 pi in IFN-γR(-/-) mouse sera. On the other hand, in the nonlethal P. yoelii 17XNL infection, WT mice could control a primary infection with 1 × 10(5) parasitized erythrocytes. Although IFN-γR(-/-) mice could not control and died with increasing parasitemia, the mice could survive by CQ treatment. Both WT and IFN-γR(-/-) mice with and without medication, which survived from P. yoelii 17XNL infection, showed the variable levels of malaria-specific IgG1, IgG2a, IgG2b, and IgG3 antibodies during the course of infection. The present data indicate that the IFN-γ receptors are needed to control the infection and parasite-specific IgG2a antibody plays an essential role in recovery from the infection of erythrocytic stages of P. yoelii 17XL or P. yoelii 17XNL parasite.

Effects of Hochu-ekki-to (TJ-41) on the course of lethal rodent malarial infection with Plasmodium chabaudi AS were examined in male A/J mice. We examined the mortality, parasitemia and serum cytokines such as IL-12, IFN-c and IL-4 in the infected and TJ-41-treated/infected mice. There was a significant difference in mortality between infected and treated/infected mice. A high mortality was observed in male mice after infection with P. chabaudi AS. In mice treated with TJ-41, control of the primary infection was achieved,and significantly lower mortality was observed. All surviving males in the treated/ infected group showed somewhat smaller peak parasitemias than those in infected controls. Mice in the infected and treated/infected groups displayed significantly elevated serum IL-12 levels on day 4 of infection when compared with the levels from the uninfected animals. Mice in the infected and treated/infected groups displayed significantly elevated serum IFN-c levels when compared with the levels from the uninfected animals. Furthermore, a significantly higher IFN-c level was seen in the treated/infected group than that in the infected group on day 4 of infection. The present results suggest that an early production of IFNc in the TJ-41-treated/infected mice is associated with a decrease of parasitemia, being responsible for the survival of mice.

A protein having Mr of more than 900K (900,000) was isolated by chromatography on a column of Sepharose 4B coupled with solubilized elastin, followed by sucrose density gradient centrifugation. The protein is composed of several disulfide-linked subunits. SDS-polyacrylamide gel electrophoresis and immunoblotting indicated that two of the subunits are identical with the heavy chains of IgM and IgG, and one is immunologically related to the heavy chain of IgA. The results suggested that this protein is a new protein that belongs to the category of, or is closely related to, the immunoglobulins. As described in the succeeding paper, it has cell-binding activity (Fukamizu et al. (1986) J. Biochem. 100, 843-848). We tentatively refer to this protein as "cell-binding immunoglobulin-like protein (CIP)."

Cell adhesion to plastic surfaces coated with a new high-molecular-mass immunoglobulin-like protein from normal human plasma was studied. Mouse subdermal fibroblasts, hamster kidney cells, human umbilical vein endothelial cells, and human skin fibroblasts were found to become attached to the surface, but cancer cells derived from human stomach cancer and human breast cancer did not. The appearance of the attached cells differed from that of cells attached to surfaces coated with fibronectin or concanavalin A. The cell adhesion to the surfaces coated with the protein was inhibited by goat anti-human IgM. Furthermore, the binding of the protein to the cell surfaces was demonstrated by the indirect immunofluorescence method. It is concluded that this protein is a new cell-binding protein.