Fc receptor-dependent activation of effector function of gnotobiotic porcine pulmonary alveolar macrophages.
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Biomedical subjects
Publications and source records attributed to R Rothlein.
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The mechanisms of cytotoxicity by porcine pulmonary alveolar macrophages (PAM) involved in antibody-dependent cellular cytotoxicity (ADCC) and immobilized immune complex-dependent cellular cytotoxicity (IIC-DCC) were investigated. The results indicate that IIC-DCC was inhibited by both catalase and thioglycollate broth whereas these peroxide scavengers had no effect on ADCC in an 18-hr chromium-release assay. Furthermore, it was found that when the PAM and red blood cell targets were cross-linked with PHA, catalase still completely eliminated IIC-DCC and had no effect on ADCC, which suggests that catalase is able to penetrate the lytic site when the effector and targets are cross-linked as in ADCC. The presence of cytochalasin B, which inhibits internalization of immune complexes by PAM and presumably prevents intracellular killing, also had no effect on the differential susceptibility of IIC-DCC and ADCC to catalase. Finally, it is shown that the nonspecific cytotoxicity generated by exposing PAM to immune complexes in suspension in conjunction with cytochalasin B, so that the immune complex-bound Fc receptor (FcR) cannot be internalized, also was susceptible to catalase. These data show that the lytic mechanism involved in the nonspecific cytotoxicity generated by exposing PAM to immobilized immune complexes or immune complexes in suspension in conjunction with cytochalasin B, both of which prevent the internalization of immune complex-bound FcR, is mediated solely by peroxide whereas the lytic mechanism involved in ADCC operates, at least partially, through a peroxide-independent mechanism.
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In this study, the average percentage of bovine spleen and lymph node cells with surface immunoglobulin (S-Ig) was found to be 19.62 and 23.18%, respectively. The average percentage of these cells with cytoplasmic immunoglobulin (C-Ig) was 14.46 and 17.21%. Only the percentage of cells with S-Ig showed a strong correlation between the spleen and the lymph node. Also, several methods of removing S-Ig from bovine peripheral blood mononuclear cells were investigated. It was found that the loss of passively bound S-Ig by warm washing was minimal, and that the anti-Ig-treated mononuclear blood cells would lose their caps after 24 h of incubation at 37 degrees C, but not after 45 min of incubation, although 95% of the cells with S-Ig were capped within 15 min.
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Intercellular adhesion molecule 1 (ICAM-1), a ligand of leukocyte function associated antigen 1 (LFA-1), is present on many cells, including monocyte/macrophages. ICAM-1 is considered to play an important role in the induction and maintenance of inflammatory responses by permitting leukocyte adhesion. Its expression is inducible on endothelial and epithelial cells exposed to various inflammatory cytokines (preceding expression of HLA-DR) and is maturation dependent in certain cell lines. The distribution of ICAM-1 in decidua and placenta was evaluated using peroxidase-antiperoxidase immunohistochemistry. In decidua of first and third trimesters, scattered ICAM-1-staining cells were observed. In placentas of first and third trimesters, all types of trophoblasts stained negatively for ICAM-1. Prior to 10 weeks of gestation, the villous stroma was uniformly ICAM-1 and HLA-DR unreactive. Beginning in the chorionic plate at approximately 10 weeks, scattered ICAM-1-positive stromal cells were observed, whereas stromal cells of the terminal villi revealed no ICAM-1. By 14-16 weeks, approximately 40-50% of the terminal villous stromal cells were ICAM-1 staining. This parallels the 40-50% of the villous stromal cells that share other immunohistochemical markers, such as EB-11, with monocyte/macrophages. The lack of functional maturation of the villous stromal macrophage may explain the rarity of chronic villitis early in gestation.
Noninvasive methods to assess immune activation would be helpful in optimizing therapy after heart transplantation to reduce rejection (acute and chronic) and complications caused by excessive immunosuppressive therapy. Intercellular adhesion molecule 1 has been shown to play an important role in T-cell activation and allograft rejection. A soluble form of intercellular adhesion molecule 1 has been discovered to be circulating in plasma. To test the hypothesis that increased levels of circulating intercellular adhesion molecule 1 may have prognostic value as a marker of immune activation, we examined whether levels of circulating intercellular adhesion molecule 1 during the early postoperative period correlated with endomyocardial biopsy scores, soluble interleukin-2 receptor levels, human leukocyte antigen mismatch, and survival. For the first 3 weeks after surgery, serum was obtained once weekly on the same day as endomyocardial biopsy samples from 52 patients who survived more than 30 days after heart transplantation. A sandwich enzyme-linked immunosorbent assay was used to measure circulating intercellular adhesion molecule 1 and soluble interleukin-2 receptor. Increased circulating intercellular adhesion molecule 1 levels did not correlate with endomyocardial biopsy scores but were associated with greater mismatch at the human leukocyte antigen-B and -DR loci (p = 0.02). A significant correlation was found (p = 0.002) between circulating intercellular adhesion molecule 1 levels and soluble interleukin-2 receptor, albeit with a low r value of 0.27. Survival was reduced in patients with high levels of circulating intercellular adhesion molecule 1 (p = 0.006) or soluble interleukin-2 receptor (p = 0.001) with the greatest reduction in survival when both were elevated.(ABSTRACT TRUNCATED AT 250 WORDS)