Immunostimulating Factor Isolated from Actinobacillus actinomycetemcomitans Stimulates Monocytes and Inflammatory Macrophages

Abstract

Abstract:Immunostimulating factor (ISTF) isolated from Actinobacillus actinomycetemcomitans which has been described previously, is distinct from lipopolysaccharide and induces proliferation of B cells. This study was undertaken to investigate whether ISTF might enhance the stimulation of other immune cells. Immunohistochemically, ISTF exhibited a profound stimulating effect on macrophages and dendritic cells as well as B cells in the spleen of BALB/c mice. ISTF was also recognized for its capacity to induce direct activation of mouse macrophages to produce IL-6, TNF-␣, and NO and MHC class II expression. Therefore, it is postulated that ISTF stimulates macrophages and possibly other cells to produce a wide variety of proinflammatory mediators, which may be involved in the chronicity and tissue destruction of periodontal disease.

Anti‑4‑1BB antibody‑based combination therapy augments antitumor immunity by enhancing CD11c+CD8+ T cells in renal cell carcinoma

“…on days 3, 7 and 12, and anti-4-1BB mAb (3E1) was injected i.p. on days 7 and 12, while a control group received PBS and rat IgG ( 16 , 27 ). The tumor diameter was measured every 2–3 days, and the tumor volume (in mm 3 ) was calculated using a caliper.…”

“…The immunostimulatory factor (ISTF; 13 kDa) isolated from A. actinomycetemcomitans , has potent mitogenic activity on mouse B cells and human peripheral blood mononuclear cells ( 26 ). ISTF has been reported to stimulate macrophages and dendritic cells in the spleens of BALB/c mice and also has the ability to induce the direct activation of mouse macrophages to induce IL-6, TNF-α, nitric oxide and major histocompatibility complex (MHC) class II expression ( 27 ). In addition, ISTF is a proteinaceous material that directly induces the proliferation of B lymphocytes, but does not affect the proliferation of T lymphocytes, even in the presence of antigen-presenting cells (APCs) ( 26 ).…”

“…In the absence of co-stimulatory signals, antigen presentation induces T cell anergy, while co-stimulatory signals activate non-responding tumor-specific T cells ( 29 ). ISTF is expected to be highly active against APCs, and anticancer activity can be expected to be increased by the amplification of the overall immune response ( 27 ). Therefore, in the present study it was hypothesized that a combination of ISTF, promoting antigen presentation, and 4-1BB mAbs, stimulating T cell co-stimulation signals, could increase T cell activity to eradicate RCC.…”

Effect of Colchicine on Inducible Nitric Oxide Synthase Activity and Nitric Oxide Production of Mice Induced by <i>Aggregatibacter actinomycetemcomitans</i>

“…Increased expression of iNOS in inflamed periodontal tissues in humans [15] [16] and in experimental periodontitis in animal models [17] [18] have been documented, suggesting that oral bacteria, such as Aggregatibacter actinomycetemcomitans [19], inducing periodontal tissue destruction may be responsible for the increased periodontal tissue-derived iNOS expression. Indeed, A. actinomycetemcomitans induced the production of NO by both murine macrophages [20] [21] [22] [23] and splenocytes [24] as well as human osteoblasts [25]. The induction of immune response to A. actinomycetemcomitans in mice both in vivo and in vitro was regulated by NO [26] [27] [28] [29].…”

Biological Characterization of the Omp1-like Protein from Actinobacillus actinomycetemcomitans

“…3 In particular, the pathogenesis of periodontitis might be explained by immune stimulation by periodontopathic bacteria, which induce large scale T cell activation, cytokine production and polyclonal B cell activation. 4 The N-terminal amino acid sequence of outer membrane protein Omp26 (202 aa) from Nontypeable Haemophilus influenzae has a revealed homology to a Yersinia enterocolitica OmpH, as well as homologies to Skp (17 kDa), OmpH, and Hip-1 proteins in Pasteurella multocida, Yersinia pseudotuberculosis, Escherichia coli and Salmonella enterica. 5 Seventeen kilodalton protein (Skp) has been characterized as a molecular chaperone that interacts with unfolded proteins as they emerge in the periplasm from the Sec translocation machinery.…”