The N-terminal of thrombospondin-1 is essential for coagulase-negative staphylococcal binding

Bacterial binding was studied to determine whether thrombospondin-1 (TSP) acts as a ligand in attachment of coagulase-negative staphylococci (CNS). Twenty-five of 27 CNS strains bound soluble TSP. Staphylococcus epidermidis J9P bound 125I-labelled TSP in a dose-dependent manner. Scatchard plot analysis of the binding of TSP by strain J9P revealed two Kd values of 6.4x10-95muM and 2.9x10-85muM. The binding structures of strain J9P were sensitive to protease and were resistant to heat treatment. Unlabelled TSP and recombinant von Willebrand factor inhibited binding of TSP by strain J9P, but other proteins or monosaccharides did not. Heparin inhibited binding of TSP to strain J9P and two other S. epidermidis strains, BD5703 and BD969. Fusion proteins of the type 1 repeats, type 2 repeats, type 3 repeats and C-terminal domain of TSP or the synthetic Arg-Gly-Asp peptide did not inhibit binding of TSP to bacteria. TSP promoted adhesion of S. epidermidis strains when it was immobilised on polymer surfaces. These results indicate that the specific interaction between CNS and TSP may contribute to bacterial adhesion on biomaterial surfaces. The N-terminal heparin-binding domain of TSP appears to be the major region for recognition by CNS

Secondary Publication: SARS-CoV-2 and Immunological Response

Viruses require the host cellular machinery for protein translation and replication. Upon proliferation, virions damage cells and are released from the infected cells before infecting other cells. Acute inflammation occurs when host cells are damaged by infection. The cell receptors to which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) binds, are widely distributed compared to those for other viruses, thereby resulting in various symptoms such as rhinitis, pneumonia, and enteritis. In general, RNA viruses, including SARS-CoV-2, exhibit a high frequency of gene mutations. Antigenic modulation due to genetic mutations of the spike protein causes cytokine storms because of strong activation of the innate immune system, similar to the phenomenon previously observed in highly pathogenic avian influenza. The proportion of severely ill patients due to coronavirus disease 2019 (COVID-19) varies from country to country, and factors that are responsible for the severity of the disease include antibody-dependent enhancement (ADE), Bacillus Calmette-Guérin (BCG) vaccination, and human leukocyte antigen (HLA) type. ADE and HLA types may also influence the protective effect of immunity, including its vaccine response against SARS-CoV-2.This report is a secondary publication of our previous review report "Tokyo Wom Med Univ 91: 2-10, 2021.&quot

Commensal Flora, is it an Unwelcomed Companion as a Triggering Factor of Autoimmune Pancreatitis?

The etiopathogenesis of many autoimmune disorders has not been identified. The aim of this paper is to focus on the involvement of bacterial exposure, as an environmental factor, in the pathogenesis of autoimmune pancreatitis (AIP), which is broadly categorized as autoimmune disorders involving pancreatic lesions. Avirulent and/or commensal bacteria, which may have an important role(s) as initiating/progressing factors in the pathogenesis of autoimmune disorder AIP, will be emphasized

Are Dysregulated Inflammatory Responses to Commensal Bacteria Involved in the Pathogenesis of Hepatobiliary-Pancreatic Autoimmune Disease? An Analysis Using Mice Models of Primary Biliary Cirrhosis and Autoimmune Pancreatitis

The etiopathogenesis of many autoimmune disorders has not been identified. The aim of this paper is to focus on the involvement of bacterial exposure in the pathogenesis of primary biliary cirrhosis (PBC) and autoimmune pancreatitis (AIP), both of which are broadly categorized as autoimmune disorders involving hepatobiliary-pancreatic lesions. Avirulent and/or commensal bacteria, which may have important role(s) as initiating factors in the pathogenesis of autoimmune disorders such as PBC and AIP, will be emphasized

In situ proliferation and differentiation of macrophages in dental pulp

The presence of macrophages in dental pulp is well known. However, whether these macrophages proliferate and differentiate in the dental pulp in situ, or whether they constantly migrate from the blood stream into the dental pulp remains unknown. We have examined and compared the development of dental pulp macrophages in an organ culture system with in vivo tooth organs to clarify the developmental mechanism of these macrophages. The first mandibular molar tooth organs from ICR mice aged between 16 days of gestation (E16) to 5 days postnatally were used for in vivo experiments. Those from E16 were cultured for up to 14 days with or without 10% fetal bovine serum. Dental pulp tissues were analyzed with immunohistochemistry to detect the macrophages and with reverse transcription and the polymerase chain reaction (RT-PCR) for the detection of factors related to macrophage development. The growth curves for the in vivo and in vitro cultured cells revealed similar numbers of F4/80-positive macrophages in the dental pulp. RT-PCR analysis indicated the constant expression of myeloid colony-stimulating factor (M-CSF) in both in-vivo- and in-vitro-cultured dental pulp tissues. Anti-M-CSF antibodies significantly inhibited the increase in the number of macrophages in the dental pulp. These results suggest that (1) most of the dental pulp macrophages proliferate and differentiate in the dental pulp without a supply of precursor cells from the blood stream, (2) M-CSF might be a candidate molecule for dental pulp macrophage development, and (3) serum factors might not directly affect the development of macrophages

Outer Membrane Protein of Gut Commensal Microorganism Induces Autoantibody Production and Extra-Intestinal Gland Inflammation in Mice

Gut commensal microorganisms have been linked with chronic inflammation at the extra-intestinal niche of the body. The object of the study was to investigate on the chronic effects of a gut commensal Escherichia coli on extra-intestinal glands. The presence of autoimmune response was diagnosed by autoantibody levels and histological methods. Repeated injection of E. coli induced mononuclear cell inflammation in the Harderian and submandibular salivary glands of female C57BL/6 mice. Inflammation was reproduced by adoptive transfer of splenocytes to immune-deficient Rag2 knockout mice and CD4+ T cells to mature T cell-deficient TCRβ-TCRδ knockout mice. MALDI TOF mass spectrometry of the protein to which sera of E. coli-treated mice reacted was determined as the outer membrane protein A (OmpA) of E. coli. Multiple genera of the Enterobacteriaceae possessed OmpA with high amino-acid sequence similarities. Repeated injection of recombinant OmpA reproduced mononuclear cell inflammation of the Harderian and salivary glands in mice and elevation of autoantibodies against Sjögren’s-syndrome-related antigens SSA/Ro and SSB/La. The results indicated the possibility of chronic stimuli from commensal bacteria-originated components as a pathogenic factor to elicit extra-intestinal autoimmunity

Secondary Publication: SARS-CoV-2 and Immunological Response

Viruses require the host cellular machinery for protein translation and replication. Upon proliferation, virions damage cells and are released from the infected cells before infecting other cells. Acute inflammation occurs when host cells are damaged by infection. The cell receptors to which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) binds, are widely distributed compared to those for other viruses, thereby resulting in various symptoms such as rhinitis, pneumonia, and enteritis. In general, RNA viruses, including SARS-CoV-2, exhibit a high frequency of gene mutations. Antigenic modulation due to genetic mutations of the spike protein causes cytokine storms because of strong activation of the innate immune system, similar to the phenomenon previously observed in highly pathogenic avian influenza. The proportion of severely ill patients due to coronavirus disease 2019 (COVID-19) varies from country to country, and factors that are responsible for the severity of the disease include antibody-dependent enhancement (ADE), Bacillus Calmette-Guérin (BCG) vaccination, and human leukocyte antigen (HLA) type. ADE and HLA types may also influence the protective effect of immunity, including its vaccine response against SARS-CoV-2.This report is a secondary publication of our previous review report "Tokyo Wom Med Univ 91: 2-10, 2021.&quot

Protein adsorption on ex vivo catheters and polymers exposed to peritoneal dialysis effluent.

medical devices has been recognized to putatively relate to the process of regulation of biomaterial-associated complications by attachment of fibrin clots, eukaryotic cells, and microbes. The molecules adsorb to a varying extent, depending not only on the physicochemical prop-erties of the biomaterial, but also on the composition of the host fluid. ♦ Objective: Adsorption of proteins on catheters exposed both ex vivo and in vitro to dialysate of patients on peri-toneal dialysis (PD) was studied. ♦ Methods: Peritoneal dialysis effluent was collected from 5 patients with end-stage renal disease on continu-ous ambulatory PD. Tenckhoff catheters were obtained from 16 patients. Deposition of proteins on excised Tenck-hoff catheters and tubing of different materials expose