Biological effects of individually synthesized TNF-binding domain of variola virus CrmB protein.

The biological characteristics of a 17-kDa protein synthesized in bacterial cells, a TNF-binding domain (VARV-TNF-BP) of a 47-kDa variola virus CrmB protein (VARV-CrmB) consisting of TNF-binding and chemokine-binding domains, were studied. Removal of the C-terminal chemokine-binding domain from VARV-CrmB protein was inessential for the efficiency of its inhibition of TNF cytotoxicity towards L929 mouse fibroblast culture and for TNF-induced oxidative metabolic activity of mouse blood leukocytes. The results of this study could form the basis for further studies of VARV-TNF-BP mechanisms of activity for prospective use in practical medicine.

Peculiarities of bone marrow hemopoiesis in early aging OXYS rats.

Colony-forming activity of bone marrow cells in 3- and 12-month-old Wistar rats does not differ by the number of early and erythroid precursors and by the formation of granulocyte-macrophage colonies. In senescence-accelerated OXYS rats, the number of early and erythroid precursors significantly increases by the age of 12 months and surpasses the corresponding values in Wistar rats. The number of granulocyte-macrophage colonies in OXYS rats does not change with age, but the numbers of these colonies formed at the age of 3 and 12 months in these animals are higher than in Wistar rats. As a result, the total number of hemopoietic colonies in 12-month-old OXYS rats 2-fold surpassed that in 12-month-old Wistar rats. Activation of granulopoiesis and increased numbers of early and erythroid precursors indicate deep changes in the functional status of the hemopoietic stem cell in 1-year-old OXYS rats in the direction characteristic of aging animals.

Cell cycle of bone marrow CD34+ cells during autoimmune disease development in MRLMpJ/lpr mice.

The development of autoimmune disease in Fas-deficient MRLMpJ/lpr mice is associated with a relative decrease in the content of bone marrow CD34+ cells, which can attest to intensification of migration of early hemopoietic precursors from the bone marrow. The intensity of CD34+ apoptosis is high in young healthy MRLMpJ/lpr mice in comparison with the control, but decreases during the development of autoimmune disease. Proliferative activity of CD34+ cell population surpassed the control in all mouse groups, except AID2. The detected shifts in quantitative and qualitative parameters of CD34+ cells attest to an important role of stem hemopoietic precursors in the formation of autoimmune disease in MRLMpJ/lpr mice.

Formation of immunodeficiency in newborn mice exposed to nicotine during intrauterine development.

Exposure to nicotine during intrauterine development leads to immunodeficiency manifested in inhibition of delayed-type hypersensitivity reaction and reduced number of antibody-producing cells forming in response to sheep erythrocytes in newborn mice. The number of splenic CFU in the bone marrow of newborn mice exposed to nicotine in utero is decreased compared to the control. By contrast, nicotine induced an increase in splenic CFU count in fetal liver. We concluded that nicotine modifying the hemopoietic microenvironment delayed the release of primitive precursors from fetal liver, which impaired colonization of fetal bone marrow and led to imbalance in the production of mature blood cell, including immune system cells.

DNA-hydrolyzing antibodies from sera of autoimmune-prone MRL/MpJ-lpr mice.

Catalytically active antibodies (abzymes) hydrolyzing proteins, polysaccharides, ATP, DNA, and RNA have been detected in the sera of patients with various autoimmune and some viral diseases, but abzymes from the sera of animals are practically unstudied. The development of lupus-like autoimmune disease of MRL/MpJ-lpr mice is an experimental model for study of autoimmune pathologies and immunopathogenesis. In this work, homogeneous IgG preparations were isolated from the sera of MRL/MpJ-lpr mice. These antibodies (Abs), their Fab-fragments, and isolated light chains were shown to possess catalytic activity in DNA hydrolysis, whereas Abs from the sera of control healthy mice did not hydrolyze DNA. The data demonstrate that DNA hydrolyzing activity is an intrinsic property of Abs from MRL/MpJ-lpr mice. It was shown that various markers of autoimmune pathologies (level of total protein concentration in urea (proteinuria), Abs titers to native and denatured DNA, and DNA-hydrolyzing activity of IgG) increased in animals with aging, but they noticeably increased (2-22 times) only after appearance of obvious indicators of pathology independently of age. The highest increase in proteinuria (25-fold), anti-DNA Abs titers (12-19-fold), and abzyme activity (120-fold) was found in mice after their immunization with DNA-protein complex.

Effects of prenatal hypoxia on the formation of immune deficiency in newborn mice.

Fetal hypoxia in the II trimester of pregnancy caused immunodeficiency in newborn mice: inhibition of antibody production to sheep erythrocytes and disturbances in migration of early hemopoietic precursors from the bone marrow to the spleen.

The effect of haemopoietic stem cell proliferation on the humoral immune response in mice.

A study was made of the effect of humoral factors, isolated from bone marrow cell (BMC) supernatant fluid and capable of modifying CFU-S proliferation, on the generation of IgM plaque-forming cells (PFC) against sheep red blood cells (SRBC) in mice after adoptive transfer. Adoptive transfer of BMC, preincubated with the humoral factor RBME-III, which stimulates CFU-S proliferation, was shown to suppress the splenic PFC generation in recipients; treatment of BMC with a further factor NBME-IV, which inhibits CFU-S proliferation, was followed by augmentation of PFC generation. Similar effects were obtained while studying the IgM PFC generation in the bone marrow of mice after secondary immunization when relevant factors were injected, in vivo, 24 hr following primary immunization. The results of adoptive transfer experiments indicate that populations of T- and B-cells are not the targets for the action of CFU-S proliferation regulatory factors. These factors are shown to modulate the erythroid differentiation of CFU-S. The possibility of quantitative modification of immune response parameters with the help of bone marrow factors that influence the proliferation and differentiation of CFU-S is discussed.