ABSTRACT
It has recently been shown that measurable amounts of complement proteins, C6 and in particular C7, are released from human polymorphonuclear leukocytes (PMNs). The aim of the present study was to investigate the impact of opsonized Candida albicans on this release. Stimulation with opsonized C. albicans led to a rapid and sustained increase of C6 and C7 in the cell culture supernatant beginning within 5 min of placing in co-culture, whereas co-culture with unopsonized C. albicans or C. albicans mock-opsonized with inactivated human serum did not affect the release. In contrast, even after stimulation employing opsonized C. albicans, no release of the complement component C8 and only trace amounts of C9 were detected. The presence of the membrane attack complex (MAC) on C. albicans after opsonization was demonstrated by indirect immunofluorescence. Opsonization of C. albicans with human serum deficient in or depleted of a terminal complement component resulted in only minor stimulation of C6 and C7 release, although C3 deposition on the surface of C. albicans was not affected as determined by direct immunofluorescence. Detailed analyses with inactivated or deficient sera showed that detection of C6 and C7 was not due to insufficient washing of the opsonized yeast prior to co-culture and suggest that only a small proportion of these proteins was derived from the membrane bound and then cleaved off MAC. Thus, these findings imply that MAC on the fungal surface may represent an additional trigger for the release of C6 and C7 from PMNs, suggesting a new role for the terminal complement complex (TCC) on target membranes as modulator of PMN functions locally at the site of inflammation.
Subject(s)
Complement Membrane Attack Complex/metabolism , Complement System Proteins/metabolism , Neutrophils/immunology , Yeasts/immunology , Candida/immunology , Candida albicans/immunology , Cell Survival , Cells, Cultured , Complement C6/metabolism , Complement C7/metabolism , Fluorescent Antibody Technique, Indirect , Humans , Neutrophils/metabolism , Opsonin Proteins/immunology , Saccharomyces cerevisiae/immunology , Yeasts/metabolismABSTRACT
The putative virulence factor secreted aspartyl proteinase (SAP) of Candida albicans and the human immunodeficiency virus type 1 (HIV-1) protease both belong to the aspartyl proteinase family. The present study demonstrates that the HIV-1 protease inhibitor Indinavir is a weak but specific inhibitor of SAP. In addition, Indinavir reduces the amount of cell bound as well as released SAP antigen from C. albicans. Furthermore, viability and growth of C. albicans are markedly reduced by Indinavir. These findings indicate that HIV-1 protease inhibitors may possess antifungal activity and we speculate that in vivo SAP inhibition may add to the resolution of mucosal candidiasis in HIV-1 infected subjects.
Subject(s)
Aspartic Acid Endopeptidases/antagonists & inhibitors , Candida albicans/drug effects , HIV Protease Inhibitors/pharmacology , HIV Protease/drug effects , Indinavir/pharmacology , Amino Acid Sequence , Aspartic Acid Endopeptidases/chemistry , Candida albicans/enzymology , Candida albicans/pathogenicity , Molecular Sequence Data , VirulenceABSTRACT
Previously, it has been shown that human immunodeficiency virus (HIV)-1 envelope proteins gp160 and gp41 bind to Candida albicans. Whether this interaction affects candidal virulence in vitro was investigated. HIV-1 gp160 or gp120 treatment of C. albicans significantly altered neither growth nor phospholipase activity of the fungus. However, treatment of C. albicans with gp160, but not with gp120, led to an elevation of free and cell-bound aspartate proteinase. In addition, culture supernatants obtained from C. albicans treated with gp160 or gp41, but not with gp120, showed a strong increase in proteinase activity. Finally, C. albicans viable yeast cells treated with gp160 or gp41 and serum were phagocytosed by polymorphonuclear leukocytes to a lesser extent than was C. albicans treated with gp120 and serum or serum alone. These findings suggest that the interaction between HIV-1 gp160 and C. albicans may promote the virulence of C. albicans in HIV-1-positive patients.
Subject(s)
Candida albicans/metabolism , Candida albicans/pathogenicity , Candidiasis/pathology , HIV Envelope Protein gp120/pharmacology , HIV Envelope Protein gp160/pharmacology , HIV Envelope Protein gp41/pharmacology , Antigens, Fungal/analysis , Antigens, Fungal/immunology , Aspartic Acid Endopeptidases/metabolism , Candida albicans/growth & development , Candidiasis/immunology , Candidiasis/metabolism , Culture Media, Conditioned/chemistry , Culture Media, Conditioned/metabolism , Endopeptidases/analysis , Endopeptidases/metabolism , HIV Envelope Protein gp120/metabolism , HIV Envelope Protein gp160/metabolism , HIV Envelope Protein gp41/metabolism , Humans , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/microbiology , Neutrophils/immunology , Opsonin Proteins/pharmacology , Phagocytosis/immunology , Phospholipases/metabolism , VirulenceABSTRACT
Oral candidiasis in human immunodeficiency virus type 1 (HIV-1)-infected persons is believed to be caused by the acquired T lymphocyte immunodeficiency. The direct interaction of C. albicans and HIV-1 in vitro was investigated. Twice as many yeasts adhered to cells transfected with the HIV-1 env gene as they did to controls. HIV-1 rsgp160 and rsgp41 but not rsgp120 were found to bind to Candida albicans via two C3-like regions within gp41. Normal human serum, but not C3-depleted serum, was able to inhibit rsgp41 binding to C. albicans. Vice versa, rsgp160 and rsgp41 were able to block rosetting of C. albicans with iC3b-coated sheep erythrocytes. Binding to C. albicans, and its inhibition by rsgp41 or rsgp160, was confirmed for the whole virus. Therefore, oral candidiasis in HIV-1-infected subjects may be augmented or may even be initiated by direct interaction between C. albicans and HIV-1 or HIV-1-infected cells.
Subject(s)
Candida albicans/metabolism , Complement C3/metabolism , HIV Envelope Protein gp41/metabolism , HIV-1/metabolism , Amino Acid Sequence , Binding, Competitive , Complement C3/genetics , HIV Core Protein p24/analysis , HIV Envelope Protein gp41/genetics , HeLa Cells , Humans , Molecular Sequence Data , Recombinant ProteinsABSTRACT
Previous studies have proved that a certain acidic isoform of ferritin is specifically synthesized by the placenta and breast-cancer tissue. In this context it has been further reported that the determination of this so-called placental isoferritin (PLF) on the surface of a subset of peripheral lymphocytes is highly specific and sensitive for early stage breast cancer. By use of the monoclonal antibody CM-H-9 and flow cytometry, the levels of placental ferritin (PLF)-positive cells were determined in 133 female patients undergoing surgical excision of a controversial or highly suspicious lesion of the breast detected by mammography. In addition, 61 healthy blood donors served as controls. Values of PLF-positive cells in breast cancer patients differed significantly from those found in women with benign diseases and healthy controls (3.87% vs. 1.55% and 2.02, respectively; p less than 0.00001). Analysis of prognostic factors in breast cancer patients (tumor size, lymph-node status, menopausal status, estrogen receptor status, histologic grading and grading subfactors) revealed significantly higher levels of PLF-positive cells in lymph-node-negative patients compared with node-positive patients (p less than 0.00001). Furthermore, levels of PLF-positive cells showed a significantly negative correlation with tumor size and nuclear polymorphism. In 15 patients who underwent a guide-wire-directed surgical biopsy for a non-palpable, mammographically suspect lesion, 4 cases of cancer correlated with high values of PLF-positive lymphocytes while only 1 patient with a benign histologic result exhibited more than 4% positive cells.
Subject(s)
Breast Neoplasms/pathology , Ferritins/analysis , Lymphocytes/chemistry , Adult , Aged , Cell Nucleus , Female , Humans , Middle Aged , Neoplasm Staging , Placenta/chemistry , Polymorphism, Genetic , PrognosisABSTRACT
A study was initiated to assess the significance of antibody to hepatitis Be antigen (anti-HBe) in HBsAg-negative individuals. Anti-HBe was demonstrated in the majority of sera positive for anti-HBs and anti-HBc. All sera positive for anti-HBs and negative for anti-HBc and most sera positive for anti-HBc but negative for anti-HBs were anti-HBe-negative. This implies that the antibody response to HBeAg is of shorter duration than that to HBsAg and HBcAg. Anti-HBe may help to discriminate between various states of hepatitis B virus infection found to be associated with anti-HBc-positive but HBsAg- and anti-HBs-negative sera. 2 individuals were anti-HBe-positive but HBsAg-, anti-HBs- and anti-HBc-negative, this finding is not understood.
Subject(s)
Antibodies, Viral , Hepatitis B Antibodies , Hepatitis B Antigens/immunology , Hepatitis B Surface Antigens , Hepatitis B e Antigens/immunology , Antigen-Antibody Reactions , Hepatitis B Antibodies/biosynthesis , Hepatitis B Core Antigens/immunology , HumansABSTRACT
The present study was initiated to assess the risk of infection of medical personnel and family contacts of hemodialysis patients. It confirms previous reports that hemodialysis patients and staff members of hemodialysis units are at high risk of acquiring HBV infection. Approximately 25% of the household contacts had serological signs of past or ongoing HBV infections. The risk of infection of the family contact was independent of the mode of dialysis but increased if the contact was a spouse, assisted in dialysis, or if the index hemodialysis patient was HBsAg positive. There is an urgent need for active immunization to prevent spread of HBV related to hemodialysis.
