muramidase and Brucellosis

Brucella abortus injected into CBA mice replicated primarily in the spleen and liver, reaching a peak bacterial count in both organs about 7 days postinfection. The organism was eliminated from the liver but declined to a chronic phase in the spleen. The infection caused hepatosplenomegaly. An influx of macrophages into the two organs was monitored by quantitative Northern (RNA blot) analysis of the macrophage-specific marker lysozyme mRNA. Lysozyme mRNA was detectable in spleen and increased three- to fourfold during infection. In liver, lysozyme mRNA was initially undetectable, but at about the peak of infection it reached a level comparable to that in the spleen. Macrophage colony-stimulating factor 1 (CSF-1) has been reported to be elevated in the circulation of animals infected with B. abortus and is known to stimulate monocytopoiesis. To investigate the role of CSF-1 in pathogenesis, we studied the effect of further increasing the CSF-1 concentration by administration of recombinant human CSF-1. Since the infection is characterized by several distinct phases, recombinant human CSF-1 was administered at defined times relative to these phases. Pronounced effects were observed only when CSF-1 administration was begun during the developing acute phase. The consequences were decreased bacterial numbers in the spleen but an increase in the liver, reduced antibody generation, and increased hepatosplenomegaly. A feature of many chronic intracellular infections is immunosuppression. B. abortus caused a substantial diminution of responsiveness of spleen cells to T-cell mitogens, particularly concanavalin A. This action was mimicked by CSF-1 treatment of the animals prior to spleen cell isolation. The results suggest that CSF-1 plays a role in macrophage recruitment in brucellosis and that recruited macrophages contribute to the immunopathology and immunosuppression.

Topics: Animals; Antibody Formation; Blotting, Northern; Brucellosis; Colony-Forming Units Assay; Disease Models, Animal; Dose-Response Relationship, Immunologic; Hepatomegaly; Hypersensitivity, Delayed; Liver; Lung; Lymphocyte Activation; Macrophage Colony-Stimulating Factor; Macrophages; Mice; Mice, Inbred CBA; Muramidase; Organ Size; Recombinant Proteins; RNA, Messenger; Spleen; Splenomegaly; Time Factors

Macrophage spreading, surface receptor density/avidity, phagocytosis, random migration, chemotactic responsiveness, and serum lysozyme were examined during the course of infection (up to 60 days) of mice with Brucella abortus strain 19. Markedly enhanced in vitro spreading activity was observed throughout the period of study. The density/avidity of cell surface immunoglobulin G Fc receptors was increased for up to 60 days postinfection. Internalization of sheep erythrocytes via C3 receptors was significantly enhanced. Random locomotion and chemotactic responsiveness to lymphocyte-derived chemotactic factor and N-formyl-L-methionyl-L-leucyl-L-phenylalanine were markedly stimulated. Serum lysozyme was also elevated in infected animals. These changes indicated significant and prolonged enhancement of macrophage activity during Brucella infection. These findings are discussed in relation to previous reports describing macrophage activation by Brucella.

Topics: Animals; Brucella abortus; Brucellosis; Cell Movement; Chemotaxis; Immunity; Macrophages; Mice; Mice, Inbred C57BL; Muramidase; Phagocytosis; Receptors, Fc

Lysozyme content was determined in the subcutaneous cellular tissue of guinea pigs and albino rats differing by species resistance to brucella infection. Experiments were conducted on intact animals and those inoculated subcutaneously with live Br. abortus 19-BA vaccine. Connective tissue was taken from the site of the vaccine administration and from the contralateral side (control). Observations showed connective tissue of the animals highly sensitive to brucella infection to be exceedingly poor in this enzyme; as to connective tissue of albino rats with low sensitivity--it contained high amount of this enzyme. Lysozyme content increased considerably in the animals belonging to both species in the inflammatory focus developing at the site of the vaccine inoculation.

Topics: Animals; Brucella abortus; Brucellosis; Connective Tissue; Guinea Pigs; Muramidase; Rats; Species Specificity; Vaccination

Topics: Adult; Anti-Bacterial Agents; Ascorbic Acid; Brucellosis; Chronic Disease; Drug Hypersensitivity; Female; Humans; Immunotherapy; Male; Middle Aged; Muramidase; Oleandomycin; Phagocytosis; Physical Therapy Modalities; Pigments, Biological; Prodigiosin; Pyrroles; Serratia marcescens; Stimulation, Chemical; Tetracycline; Vitamins

Topics: Animals; Brucella Vaccine; Brucellosis; Guinea Pigs; Humans; Muramidase; Saliva; Vaccination

Topics: Acute Disease; Adolescent; Adult; Aged; Brucellosis; Chronic Disease; Female; Hemagglutination Tests; Humans; Immunoglobulin M; Immunotherapy; Male; Middle Aged; Muramidase; Vaccines

Topics: Adolescent; Adult; Aged; Brucellosis; Child; Child, Preschool; Female; Humans; Male; Methacycline; Middle Aged; Muramidase

Topics: Animals; Brain; Brucella abortus; Brucellosis; Guinea Pigs; Liver; Muramidase; Spleen; Vaccination

Topics: Agglutinins; Anti-Infective Agents, Local; Blood Proteins; Brucellosis; Humans; Muramidase; Typhoid Fever