Journal Article•
Activation of Normal Rabbit Macrophage Monolayers by Supernatants of Antigen-Stimulated Lymphocytes
01 Nov 1970-Journal of Immunology (American Association of Immunologists)-Vol. 105, Iss: 5, pp 1138-1145
TL;DR: Macrophages exposed to supernatants from mixtures of sensitized cells with specific antigen had two to five times greater numbers of ameboid cells at 24 and 48 hr than did monolayers of the same macrophage exposed to control supernatant, and twice as many cells remained adherent at 48 hr.
Abstract: Tuberculin- or HSA-sensitized rabbit lymph node cells, harvested at 10 to 14 days, and normal rabbit lymph node cells were incubated for 24 hr alone or in the presence of specific or heterologous antigen. The supernatants prepared from these lymph node cell cultures were added to duplicate or triplicate monolayer cultures of peritoneal macrophages from normal rabbits, each macrophage being exposed to soluble products released in vitro by 10 lymph node cells. After 24 and 48 hr of continuous exposure to the undiluted supernatants, 150 to 300 cells in each flask were scored for adherence and ameboid activity. Macrophages exposed to supernatants from mixtures of sensitized cells with specific antigen had two to five times greater numbers of ameboid cells at 24 and 48 hr than did monolayers of the same macrophages exposed to control supernatants, and twice as many cells remained adherent at 48 hr. Thus, factors released by sensitized lymphocytes cause activation of normal macrophages. It is suggested that a similar mechanism may be responsible for cell-mediated immunity in systems involving microbial antigens.
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TL;DR: It is concluded that LAF stimulates both central and peripheral T lymphocytes and enhances their responses to other stimulants.
Abstract: Effective supernatants (SUP), which potentiate mouse T-cell responses to phytohemagglutin (PHA), are obtained from cells of several species (human, rabbit, rat, mouse) and indeed from syngeneic spleen, thymus, or bone marrow cells. Unstimulated cells release some SUP activity but more is produced after stimulation. Lipopolysaccharide (LPS) produced very active SUP in all cultures tested. PHA was similarly active on human leukocytes only, whereas concanavalin A (Con A) gave highly efficient SUP only with mouse spleen cells. SUP production is not correlated with a mitotic response of the donor cells and is observed in cultures unable to respond mitotically to the stimulant. Adherent mouse spleen cell populations, consisting largely or entirely of macrophages, produce active SUP, while nonadherent cells do not. Similarly, purification of human peripheral leukocytes on nylon columns, with removal of macrophages and other adherent cells, destroys their ability to produce SUP. The importance of indirect effects in stimulating mitotic responses of T cells is emphasized by the fact that the mitotic response of mouse thymocytes to LPS and its ability to potentiate the response of these cells to PHA disappears with removal of adherent cells from the thymocyte population. Conversely the production of SUP from spleen cells stimulated by Con A requires the presence of T cells.
726Â citations
TL;DR: Macrophage adherence, phagocytosis, spreading, motility, and direct hexose monophosphate oxidation were enhanced, while protein synthesis was unaffected, so antigen-stimulated lymphocytes secrete a factor or factors which enhance certain macrophage functions.
Abstract: Sensitized lymphocytes were incubated in vitro with the specific antigen Supernatants from these cultures were chromatographed on Sephadex G-100 columns. Supernatant fractions containing MIF, chemotactic factor, and lymphotoxin, but free of antigen and antibody, were incubated with normal peritoneal exudate macrophages. Macrophage adherence, phagocytosis, spreading, motility, and direct hexose monophosphate oxidation were enhanced, while protein synthesis was unaffected. Thus, antigen-stimulated lymphocytes secrete a factor or factors which enhance certain macrophage functions. Implications for models of cellular immunity and cellular hypersensitivity are discussed.
485Â citations
Cites result from "Activation of Normal Rabbit Macroph..."
...This finding resembles that of Mooney and Waksman (35), who incubated rabbit macrophages for 24-48 hr in whole supernatants from antigen-stimulated lymph node cells and observed more macrophage adherence and spreading than after incubation in supernatants of lymph node cell cultures from unsensitized donors....
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Abstract: Recent research on human macrophage activation has reemphasized the critical role of the lymphokine-secreting T cell in converting quiescent macrophages to efficient microbicidal phagocytes. Interferon-gamma, a key lymphokine secreted by antigen-triggered T4+ helper cells, is capable of inducing the macrophage to act against a diverse group of microbial targets, in particular, intracellular pathogens. In animal models, treatment with recombinant interferon-gamma is beneficial in systemic intracellular infections, and inhibition of endogenous interferon-gamma activity impairs host resistance. Trials in patients with cancer, leprosy, and the acquired immunodeficiency syndrome (AIDS) have shown that interferon-gamma can activate the mononuclear phagocyte in humans. This research and the identification of patients whose T cells fail to produce interferon-gamma properly has set the stage for evaluating the role of macrophage-activating immunotherapy using interferon-gamma in various human infectious diseases.
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TL;DR: The intestinal lymphocyte population, in comparison with that of peripheral blood, had greater numbers of bone marrow-derived cells, particularly cells bearing membrane IgA; showed spontaneous association with macrophages; underwent rapid rosette formation with sheep erythrocytes; and demonstrated increased in vitro synthesis of immunoglobulin.
Abstract: Viable suspensions of human colonic mucosal lymphoid cells have been prepared by sequential treatment of tissue with dithiothreitol, EDTA in calcium- and magnesium-free salt solutions, and purified collagenase. The intestinal lymphocyte population, in comparison with that of peripheral blood, had greater numbers of bone marrow-derived cells, particularly cells bearing membrane IgA; showed spontaneous association with macrophages; underwent rapid rosette formation with sheep erythrocytes; and demonstrated increased in vitro synthesis of immunoglobulin. Total thymus-derived cells were equal in the two populations. Decreases were found in "null" cell numbers, in cells bearing membrane IgD and IgM, and in responsiveness to phytohemagglutinin. Macrophage/monocytes in the intestinal population were increased in size, granularity, motility, sustained glass adherence, and phagocytic activity. Human intestinal lymphoid cells appear to constitute a cell population that is more "mature" and/or "activated", in comparison with the lymphoid cells of peripheral blood. The method of preparation should lend itself to the study of inflammatory bowel disease, gastrointestinal cancer, and the intestinal secretory immune system.
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TL;DR: The virulence of periodontopathic bacteria relates to their leukaggressive properties, allowing them to evade neutrophil protective mechanisms, and the various host responses as they may affect each of these four stages are considered.
Abstract: Great progress has been made in our understanding of the pathogenesis of periodontal disease, the primary role of bacteria as etiologic agents, and the critical modifying role of host responses. It is useful to consider several stages in the pathogenesis of periodontal disease - (a) colonization, (b) invasion, (c) destruction, and (d) healing - and to place into perspective the various host responses as they may affect each of these four stages (Table 5). With respect to colonization, although very little direct evidence is available, it is reasonable to suggest that antibodies, either secretory or serum-derived, acting by virtue of their ability to block attachment, could inhibit colonization by immune reduction of adherence mechanisms. With respect to invasion of the tissue, it appears that phagocytes, particularly the neutrophils, are important, acting in concert with opsonic antibody and complement in ingesting and killing the periodontal microflora before or during the early invasive process. A major advance in our understanding of the pathogenesis of periodontal diseases is the realization that the virulence of periodontopathic bacteria relates to their leukaggressive properties, allowing them to evade neutrophil protective mechanisms. Invasion of the periodontal tissues by bacterial products may be inhibited by the complexing of these products with antibody with the formation of antigen-antibody complexes that are phagocytosed and digested, particularly by scavenger phagocytes such as the macrophage. With respect to the destructive phase of periodontal disease, it is clear that the direct effect of lymphocytes mediated either through direct cytotoxic activity, or through biologically-active destructive lymphokines (such as alpha-lymphotoxin and osteoclast activating factor), can lead to tissue destruction. Macrophages, through the production of monokines, collagenase, and reactive oxygen species, can also lead to tissue destruction. The direct effects of bacterial toxins or enzymes which can lead to tissue destruction can be inhibited by complexing with antitoxic or enzyme-neutralizing antibodies. With respect to healing and fibrosis, very little direct information is available; however, it is possible that the lymphocytes and macrophages affect fibrosis by the production of chemotactic factors for fibroblasts which would be expected to bring them to the area of periodontal inflammation and also by production of fibroblast-activating factors, which then cause the fibroblasts to proliferate and produce collagen which replaces lost collagen or results in fibrosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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