Atrophy Of White Pulp Research Articles

Vaccine Development for Severe Fever with Thrombocytopenia Syndrome Virus in Dogs.

Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening viral zoonosis. The causative agent of this disease is the Dabie bandavirus, which is usually known as the SFTS virus (SFTSV). Although the role of vertebrates in SFTSV transmission to humans remains uncertain, some reports have suggested that dogs could potentially transmit SFTSV to humans. Consequently, preventive measures against SFTSV in dogs are urgently needed. In the present study, dogs were immunized three times at two-week intervals with formaldehyde-inactivated SFTSV with two types of adjuvants. SFTSV (KCD46) was injected into all dogs two weeks after the final immunization. Control dogs showed viremia from 2 to 4days post infection (dpi), and displayed white pulp atrophy in the spleen, along with a high level of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay (TUNEL) positive area. However, the inactivated SFTSV vaccine groups exhibited rare pathological changes and significantly reduced TUNEL positive areas in the spleen. Furthermore, SFTSV viral loads were not detected at any of the tested dpi. Our results indicate that both adjuvants can be safely used in combination with an inactivated SFTSV formulation to induce strong neutralizing antibodies. Inactivated SFTSV vaccines effectively prevent pathogenicity and viremia in dogs infected with SFTSV. In conclusion, our study highlighted the potential of inactivated SFTSV vaccination for SFTSV control in dogs.

Difference in Intraspecies Transmissibility of Severe Fever with Thrombocytopenia Syndrome Virus Depending on Abrogating Type 1 Interferon Signaling in Mice.

Severe fever with thrombocytopenia syndrome (SFTS), a tick-borne zoonotic disease, is caused by infection with SFTS virus (SFTSV). A previous study reported that human-to-human direct transmission of SFTSV can occur. However, potential animal-to-animal transmission of SFTSV without ticks has not been fully clarified. Thus, the objective of this study was to investigate potential mice-to-mice transmission of SFTSV by co-housing three groups of mice [i.e., wild-type mice (WT), mice injected with an anti-type I interferon-α receptor-blocking antibody (IFNAR Ab), and mice with knockout of type I interferon-α receptor (IFNAR KO)] as spreaders or recipients with different immune competence. As a result, co-housed IFNAR Ab and IFNAR KO mice showed body weight loss with SFTS viral antigens detected in their sera, extracorporeal secretions, and various organs. Based on histopathology, white pulp atrophy in the spleen was observed in all co-housed mice except WT mice. These results obviously show that IFNAR Ab and IFNAR KO mice, as spreaders, exhibited higher transmissibility to co-housed mice than WT mice. Moreover, IFNAR KO mice, as recipients, were more susceptible to SFTSV infection than WT mice. These findings suggest that type I interferon signaling is a pivotal factor in mice intraspecies transmissibility of SFTSV in the absence of vectors such as ticks.

Alleviation of Splenic Injury by CB001 after Low-Dose Irradiation Mediated by NLRP3/Caspase-1-BAX/Caspase-3 Axis.

Low-dose radiation has been extensively employed in clinical practice, including tumor immunotherapy, chronic inflammation treatment and nidus screening. However, the damage on the spleen caused by low-dose radiation significantly increases the risk of late infection-related mortality, and there is currently no corresponding protective strategy. In the present study, a novel compound preparation named CB001 mainly constituted of Acanthopanax senticosus (AS) and Oldenlandia diffusa (OD) was developed to alleviate splenic injury caused by fractionated low-dose exposures. As our results show that, white pulp atrophy and the excessive apoptosis in spleen tissue induced by radiation exposure were significantly ameliorated by CB001. Mechanistically, BAX-caspase-3 signaling and nucleotide-binding domain and leucine-rich-repeat-containing family pyrin 3 (NLRP3) inflammasome signaling were demonstrated to be involved in the radio-protective activity of CB001 with the selective activators. Furthermore, the crosstalk between apoptosis signaling and NLRP3 inflammasome signaling in mediating the radio-protective activity of CB001 was clarified, in which the pro-apoptotic protein BAX but not the anti-apoptotic protein Bcl2 was found to be downstream of NLRP3. Our study demonstrated that the use of a novel drug product CB001 can potentially facilitate the alleviation of radiation-induced splenic injury for patients receiving medical imaging diagnosis or fractionated radiation therapy.

Intravenous Reelin Treatment Rescues Atrophy of Spleen White Pulp and Correlates to Rescue of Forced Swim Test Immobility and Neurochemical Alterations Induced by Chronic Stress

Reelin, an extracellular matrix protein with putative antidepressant-like properties, becomes dysregulated by chronic stress. Improvement in cognitive dysfunction and depression-like behavior induced by chronic stress has been reported with both intrahippocampal and intravenous Reelin treatment but the mechanisms responsible are not clear. To determine if treatment with Reelin modifies chronic stress-induced dysfunction in immune organs and whether this relates to behavioral and/or neurochemical outcomes, spleens were collected from both male (n = 62) and female (n = 53) rats treated with daily corticosterone injections for three weeks that received Reelin or vehicle. Reelin was intravenously administered once on the final day of chronic stress, or repeatedly, with weekly treatments throughout chronic stress. Behavior was assessed during the forced swim test and the object-in-place test. Chronic corticosterone caused significant atrophy of the spleen white pulp, but treatment with a single shot of Reelin restored white pulp in both males and females. Repeated Reelin injections also resolved atrophy in females. Correlations were observed between recovery of white pulp atrophy and recovery of behavioral deficits and expression of both Reelin and glutamate receptor 1 in the hippocampus, supporting a role of the peripheral immune system in the recovery of chronic stress-induced behaviors following treatment with Reelin. Our data adds to research indicating Reelin could be a valuable therapeutic target for chronic stress-related disorders including major depression.

Splenic infarction after Epstein\u2013Barr virus infection in a patient with hereditary spherocytosis: a case report and literature review

BackgroundHereditary spherocytosis (HS) complicated by splenic infarction is very rare, and it is even rarer to develop splenic infarction after infectious mononucleosis (IM) as a result of Epstein–Barr virus (EBV) infection. Therefore, misdiagnosis or missed diagnosis is prone to occur.Case presentationA 19-year-old Chinese female previously diagnosed with HS was admitted to our institution with persistent high fever and icterus. On admission, the physical examination showed anemia, jaundice, marked splenomegaly, obvious tenderness in the left upper abdomen (LUA). Peripheral blood film shows that spherical red blood cells accounted for about 6%, and Immunoglobulin M (IgM) antibodies specific to Epstein–Barr virus (EBV) viral capsid antigen were detected. An abdominal CT scan revealed a splenic infarction. The patient was diagnosed with HS with splenic infarction following EBV infection and underwent an emergency laparoscopic splenectomy (LS). Pathological analysis showed a splenic infarction with red pulp expansion, white pulp atrophy and a splenic sinus filled with red blood cells. After two months of follow-up visits, the patient showed no signs of relapse.ConclusionsHS complicated by splenic infarction is very rare and mostly occurs in men under 20 years of age and is often accompanied by other diseases, such as sickle cell traits (SCT) or IM. Although symptomatic management may be sufficient, emergency laparoscopic splenectomy may be safe and effective when conservative treatment is ineffective.

Alternariol monomethyl ether toxicity and genotoxicity in male Sprague-Dawley rats: 28-Day in vivo multi-endpoint assessment

Alternariol monomethyl ether (AME), a typical Alternaria toxin, has often been detected in grains. We have measured the general toxicity and genotoxicity of AME with a 28-day multi-endpoint (Pig-a assay + in vivo micronucleus [MN] test + comet assay) platform. Male Sprague-Dawley rats were administered AME (1.84, 3.67, or 7.35 μg/kg body weight/day), N-Ethyl-N-nitrosourea (40 mg/kg body weight/day), or corn oil by gavage for 28 consecutive days. Another group (AME-high-dose + recovery) was maintained for a further 14 days after the end of the AME administration. Hematology and serum biochemistry results suggested that AME might compromise the immune system. The histopathology results indicated that AME can cause liver (inflammatory cell infiltration, steatosis, and edema), kidney (renal glomerular atrophy), and spleen (white pulp atrophy) damage. The genotoxicity results showed that AME can induce gene mutations, chromosome breakage, and DNA damage, but the effects were diminished after the recovery period. According to point-of-departure analysis (BMDL10), the risk to the population of exposure to AME cannot be ignored and further assessment is needed.

Liver-spleen axis dysfunction in COVID-19

Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an acute infectious disease that spreads mainly through the respiratory route. Besides interstitial pneumonia, a number of other clinical manifestations were noticed in COVID-19 patients. In particular, liver and spleen dysfunctions have been described both as complications of COVID-19 and as potential predisposing factors for severe COVID-19. Liver damage is rather common in COVID-19 patients, and it is most likely multifactorial, caused by the direct insult of SARS-CoV-2 to the liver by the cytokine storm triggered by the virus, by the use of hepatotoxic drugs, and as a consequence of hypoxia. Although generally mild, liver impairment has been found to be associated with a higher rate of intensive care unit admission. A higher mortality rate was reported among chronic liver disease patients. Instead, spleen impairment in patients with COVID-19 has been poorly described. The main anatomical changes are the architectural derangement of the B cell compartment, white pulp atrophy, and reduction or absence of lymphoid follicles, while, from a functional point of view, the IgM memory B cell pool is markedly depleted. The outcome of COVID-19 in asplenic or hyposplenic patients is yet to be defined. In this review, we will summarise the current knowledge regarding the impact of SARS-CoV-2 on the liver and spleen function, as well as the outcome of patients with a pre-existent liver disease or defective spleen function.

Pathogenicity of severe fever with thrombocytopenia syndrome virus in mice regulated in type I interferon signaling

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonotic disease, which causes high fever, thrombocytopenia, and death in humans and animals in East Asian countries. The pathogenicity of SFTS virus (SFTSV) remains unclear. We intraperitoneally infected three groups of mice: wild-type (WT), mice treated with blocking anti-type I interferon (IFN)-α receptor antibody (IFNAR Ab), and IFNAR knockout (IFNAR−/−) mice, with four doses of SFTSV (KH1, 5 × 105 to 5 × 102 FAID50). The WT mice survived all SFTSV infective doses. The IFNAR Ab mice died within 7 days post-infection (dpi) with all doses of SFTSV except that the mice were infected with 5 × 102 FAID50 SFTSV. The IFNAR−/− mice died after infection with all doses of SFTSV within four dpi. No SFTSV infection caused hyperthermia in any mice, whereas all the dead mice showed hypothermia and weight loss. In the WT mice, SFTSV RNA was detected in the eyes, oral swabs, urine, and feces at 5 dpi. Similar patterns were observed in the IFNAR Ab and IFNAR−/− mice after 3 dpi, but not in feces. The IFNAR Ab mice showed viral shedding until 7 dpi. The SFTSV RNA loads were higher in organs of the IFNAR−/− mice compared to the other groups. Histopathologically, coagulation necrosis and mononuclear inflammatory cell infiltration in the liver and white pulp atrophy in the spleen were seen as the main lesions in the IFN signaling lacking mice. Immunohistochemically, SFTSV antigens were mainly detected in the marginal zone of the white pulp of the spleen in all groups of mice, but more viral antigens were observed in the spleen of the IFNAR−/− mice. Collectively, the IFN signaling-deficient mice were highly susceptible to SFTSV and more viral burden could be demonstrated in various excreta and organs of the mice when IFN signaling was inhibited.

Toxoplasma gondii causes lipofuscinosis, collagenopathy and spleen and white pulp atrophy during the acute phase of infection

In this study, we evaluated homeostatic and functional disorders of the spleen in mice inoculated with Toxoplasma gondii. The kinetics of megakaryocyte and leukocyte production, body and spleen mass and certain histopathological aspects were analyzed. There was increased (P<0.05) the accumulation of lipofuscin in the red pulp of the spleen, in the periods of 30 and 60 dpi of the infection, that is, in the chronification stage of the disease and decrease of the white pulp area. In addition, we observed (from 7dpi) a quantitative and qualitative increase (P<0.05) in the deposition of collagen fibers in the spleen of all infected mice. Since resolution of the inflammatory process resulted in pathophysiological changes, we can suggest that the T. gondii invaded and multiplied in the cells of the white and red pulps of the spleen. Although we did not find the parasite in the spleen, this hypothesis is supported by the presence of diffuse inflammatory infiltrate, which extended through the spleen parenchyma of all inoculated mice. Taken together, our results suggest that T. gondii causes severe homeostatic disorders that have altered spleen physiology, including diffuse parenchymal inflammation, lipofuscinosis in histiocytes, early aging, collagenopathy, systemic sclerosis and spleen and white pulp atrophy.

Structural changes of the spleen in experimental obesity

The paper presents and analyzes data from an experimental study conducted on white rats in females and males of reproductive age. Obesity is one of the leading causes of premature death worldwide. The purpose of the research is to establish the morphometric and histological changes of the rat spleen parenchyma in experimental obesity and after the abolition of the high-calorie diet (HCD). We conducted a study on 70 white rats of reproductive age (2.5-6.5 months) weighing 120-280 g. High-calorie diet was achieved due to the fact that food was added sodium glutamate at a dose of 67 mg/kg of body weight of the rat. Controls were 10 white rats that received a standard vivarium diet instead of a high-calorie diet. Statistical processing of digital data was performed using Excel software and STATISTICA 6.0 using the parametric methods. Eight weeks after HCD, there was a significant decrease in the relative area of white pulp in the spleen parenchyma of white rats in males and females by 16.2% and 17.4%, respectively, and an increase in the relative area of red pulp by 5.6% and 6.2%, respectively. There is an immuno-inducing effect with enhanced proliferation of activated lymphocytes and their subsequent differentiation into plasma cells. Eight weeks after the abolition of HCD, the relative area of white pulp in the spleen parenchyma of white rats in males and females was 16.8% and 16.9% less than the parameters of the intact group of animals. Accordingly, the relative area of the red pulp by 5.8% and 6.1% exceeds the parameters of the intact group of animals. The area of the lymph nodes and the size of their reproductive centers decrease. The number of monocytes, macrophages and plasmocytes increases in the organ parenchyma. Hemosiderin residues occur both in the cytoplasm of macrophages and in intercellular spaces. Arteries with thickened wall, full-blooded, veins enlarged and full-blooded. The venous sinuses of the red pulp are dilated to contain hemosiderin residues. Thus, the depletion of lymphoid tissue with progression of mainly white pulp atrophy has been established. In the conditions of the eight-week abrogation of the HCD, no reverse changes in the structure of the parenchyma of the spleen were detected.

Immunosenescence in a captive semelparous marsupial, the red-tailed phascogale (Phascogale calura)

BackgroundThe red-tailed phascogale is a ‘Near Threatened’ dasyurid marsupial. Males are semelparous and die off shortly after the breeding season in the wild due to a stress-related syndrome, which has many physiological and immunological repercussions. In captivity, males survive for more than 2 years but become infertile after their first breeding season. Meanwhile, females can breed for many years. This suggests that captive males develop similar endocrine changes as their wild counterparts and undergo accelerated aging. However, this remains to be confirmed. The health status and immune function of this species in captivity have also yet to be characterized.ResultsThrough an integrative approach combining post-mortem examinations, blood biochemical and hematological analyses, we investigated the physiological and health status of captive phascogales before, during, and after the breeding season. Adult males showed only mild lesions compatible with an endocrine disorder. Both sexes globally maintained a good body condition throughout their lives, most likely due to a high quality diet. However, biochemistry changes potentially compatible with an early onset of renal or hepatic insufficiency were detected in older individuals. Masses and possible hypocalcemia were observed anecdotally in old females. With this increased knowledge of the physiological status of captive phascogales, interpretation of their immune profile at different age stages was then attempted. During the breeding season, males developed a stress leukogram characterized by a marked lymphopenia, further aggravated by a severe leukopenia after the breeding season. To determine whether these changes were limited to the peripheral blood or had more profound implications, histopathology of the spleen was performed opportunistically. Adult males showed white pulp atrophy, at various degrees. The atrophy was mainly lymphoid and more severe in 1.5-year-old males than in 3.5-year-old females. These results suggest that captive males undergo accelerated immunosenescence.ConclusionsFunctional studies are now needed to characterize the underlying mechanisms leading to immunosenescence in marsupials. Semelparous dasyurids present great potential for studying the effects of sex and stress on immunity in marsupials. Characterization of these immune-endocrine interactions may help refine veterinary treatment plans, husbandry protocols and conservation programs to maintain the health of captive and wild populations.

Effects of dexamethasone and nimesulide on bisphosphonate-related osteonecrosis of the jaw: An experimental study

ObjectiveTo evaluate the effects of dexamethasone (DEX) and nimesulide (NIM) on Bisphosphonate-related Osteonecrosis of the Jaw (BRONJ) in rats. DesignBRONJ was induced by zoledronic acid (ZA) infusion (0.2mg/kg) in Wistar rats (n=8), followed by extraction of the left lower first molar (BRONJ groups). Control groups (n=40) received saline (IV). For eight weeks, DEX (0.04, 0.4, 4mg/kg) or saline (SAL) were administered by gavage 24h before each infusion of ZA or saline (IV), or NIM (10.3mg/kg) was administered 24h and 12h before each infusion of ZA or saline (IV). The haematological analyses were conducted weekly. After euthanasia (day 70), the jaws were submitted to radiographic and microscopic analysis. Kidney, liver, spleen and stomach were analysed histopathologically. ResultsThe BRONJ groups showed a higher radiolucent area compared with the control groups (p<0.05). Histomorphometric analysis revealed healing and new bone formation in the control groups, while the BRONJ groups exhibited devitalized bone with bacterial colonies and inflammatory infiltrate. The BRONJ-DEX 0.4 and 4mg/kg groups had a greater number of bacterial colonies (p<0.05) and an increased polymorphonuclear cell count compared to the saline-BRONJ group, while the BRONJ-NIM group had a lower polymorphonuclear count (p<0.05). The BRONJ groups had leucocytosis, which was reduced by DEX administration. Treatments with DEX with or without ZA caused white pulp atrophy. ConclusionThus, DEX or NIM therapy was not effective in preventing radiographic and histopathologic events associated with BRONJ. Treatment with DEX attenuated leucocytosis post-infusion with ZA.

Effects of purified zearalenone on selected immunological and histopathologic measurements of spleen in post-weanling gilts.

The present study was aimed at investigating the adverse effects of dietary zearalenone (ZEA) on the lymphocyte proliferation rate (LPR), interleukin-2 (IL-2), mRNA expressions of pro-inflammatory cytokines, and histopathologic changes of spleen in post-weanling gilts. A total of 20 crossbred piglets (Yorkshire × Landrace × Duroc) with an initial BW of 10.36 ± 1.21 kg (21 d of age) were used in the study. Piglets were fed a basal diet with an addition of 0, 1.1, 2.0, or 3.2 mg/kg purified ZEA for 18 d ad libitum. The results showed that LPR and IL-2 production of spleen decreased linearly (P < 0.05) as dietary ZEA increased. Splenic mRNA expressions of interleukin-1β (IL-1β) and interleukin-6 (IL-6) were linearly up-regulated (P < 0.05) as dietary ZEA increased. On the contrary, linear down-regulation (P < 0.05) of mRNA expression of interferon-γ (IFN-γ) was observed as dietary ZEA increased. Swelling splenocyte in 1.1 mg/kg ZEA treatments, atrophy of white pulp and swelling of red pulp in 2.0 and 3.2 mg/kg ZEA treatments were observed. The cytoplasmic edema in 1.1 mg/kg ZEA treatments, significant chromatin deformation in 2.0 mg/kg ZEA treatment and phagocytosis in 3.2 mg/kg ZEA treatment were observed. Results suggested that dietary ZEA at 1.1 to 3.2 mg/kg can induce splenic damages and negatively affect immune function of spleen in post-weanling gilts.

SELECTIVE INFLUENCES IN THE B-CELL RECEPTOR IMMUNOGLOBULIN HEAVY AND LIGHT CHAIN IN HAIRY CELL LEUKEMIA

Hairy cell leukemia (HCL) is a rare, chronic B-cell neoplasm characterized by leukemic hairy cells (HCs) present in blood, bone marrow, and splenic red pulp, with atrophy of white pulp. Lymph node involvement is infrequent. HCL is typically associated with markers of activation, that include expression of CD25, CD11c, FMC7, and CD103 at high intensity. A distinctive feature of HCL is expression of multiple surface immunoglobulin (sIg) isotypes, although its prevalence in HCL is not fully mapped.

3,3′-Diindolylmethane induces immunotoxicity via splenocyte apoptosis in neonatal mice

3,3′-Diindolylmethane (DIM), a major product of indole-3-carbinol derived from vegetables of the genus Brassica, exhibits chemotherapeutic activity and various immune modulatory effects in animal models and in vitro studies. Although extensive studies have only focused on DIM's beneficial effects, the toxic effects of DIM on the immune systems have not been clearly elucidated. The aim of this study was to explore the immunotoxic effects of DIM in a neonatal mouse and to further evaluate whether DIM administration affects rotavirus (RV)-induced gastroenteritis. Interestingly, multiple immunotoxic effects were observed in the DIM treated group, including decreases in various immune cells (F4/80+, CD11c+, CD19+, and CD3+ cells) in the spleen, induction of splenic white pulp atrophy, an increase in immune cell apoptosis, and decreased expression of various toll-like receptors (TLRs) in the spleen and small intestine. Apoptosis was notably promoted by up-regulating caspase-3 activity and by the change in the ratio of Bcl-2/Bax activities. Finally, oral administration of DIM led to deterioration of RV-induced intestinal disease and delayed viral clearance in the intestine and MLNs. Our results indicate that oral administration of DIM in neonatal mice induces immunotoxicity and hampers efficient RV clearance in the intestine. This new information about the immunotoxic roles of DIM in a newborn mouse model may provide valuable clues for the development of a safe supplement, especially one designed for human infants.

SELECTIVE INFLUENCES IN THE B-CELL RECEPTOR IMMUNOGLOBULIN HEAVY AND LIGHT CHAIN IN HAIRY CELL LEUKEMIA

Hairy cell leukemia (HCL) is a rare, chronic B-cell neoplasm characterized by leukemic hairy cells (HCs) present in blood, bone marrow, and splenic red pulp, with atrophy of white pulp. Lymph node involvement is infrequent. HCL is typically associated with markers of activation, that include expression of CD25, CD11c, FMC7, and CD103 at high intensity. A distinctive feature of HCL is expression of multiple surface immunoglobulin (sIg) isotypes, although its prevalence in HCL is not fully mapped.

SELECTIVE INFLUENCES IN THE B-CELL RECEPTOR IMMUNOGLOBULIN HEAVY AND LIGHT CHAIN IN HAIRY CELL LEUKEMIA

Hairy cell leukemia (HCL) is a rare, chronic B-cell neoplasm characterized by leukemic hairy cells (HCs) present in blood, bone marrow, and splenic red pulp, with atrophy of white pulp. Lymph node involvement is infrequent. HCL is typically associated with markers of activation, that include expression of CD25, CD11c, FMC7, and CD103 at high intensity. A distinctive feature of HCL is expression of multiple surface immunoglobulin (sIg) isotypes, although its prevalence in HCL is not fully mapped.

Splenic Rupture and Malignant Mediterranean Spotted Fever

Splenic Rupture and Malignant Mediterranean Spotted Fever

Vascularized bone marrow transplant (VBMT) serves as a novel surgical approach to stem cell transplantation and stimulates normal repopulation of lymphocytes in the spleens of irradiated (XRT) rat hosts

Our lab demonstrated that VBMT, the microsurgical transplantation of a femur with its vascular pedicle, can induce immune tolerance across a semi‐allogeneic barrier without graft versus host‐disease. We hypothesized that VBMT alone is potentially superior to cellular stem cell transplantation and sufficient to induce normal repopulation of the spleens of XRT rat recipients.Lewis Brown Norway rats received 9 Gy radiation. Rats then received either a conventional cellular (cBMT, n=5) or VBMT (n=4) bone marrow transplant from Lewis donors. Control groups were: non‐transplanted, non‐irradiated (CT, n= 5) or XRT only (n= 4). Stained histologic sections of spleens were analyzed with digital image analysis (DIA).XRT rats died 9±1 days post irradiation. Other groups were sacrificed: cBMT at 110 days; VBMT at 102 ±1 days. Compared to CT, XRT spleens showed white pulp atrophy; cBMT had less white pulp but appeared hypercellular and VBMT spleens appeared normal. DIA results can be seen in the table below:VBMT is capable of reconstituting spleens of XRT semi‐allogeneic recipients similar in appearance to normal rats. This model has clinical relevance for both stem cell transplantation and solid organ transplantation, in that VBMT induces chimerism and tolerance.

Pathology and Pathogenesis of Severe Acute Respiratory Syndrome

Severe acute respiratory syndrome (SARS) is an emerging infectious viral disease characterized by severe clinical manifestations of the lower respiratory tract. The pathogenesis of SARS is highly complex, with multiple factors leading to severe injury in the lungs and dissemination of the virus to several other organs. The SARS coronavirus targets the epithelial cells of the respiratory tract, resulting in diffuse alveolar damage. Several organs/cell types may be infected in the course of the illness, including mucosal cells of the intestines, tubular epithelial cells of the kidneys, neurons of the brain, and several types of immune cells, and certain organs may suffer from indirect injury. Extensive studies have provided a basic understanding of the pathogenesis of this disease. In this review we describe the most significant pathological features of SARS, explore the etiological factors causing these pathological changes, and discuss the major pathogenetic mechanisms. The latter include dysregulation of cytokines/chemokines, deficiencies in the innate immune response, direct infection of immune cells, direct viral cytopathic effects, down-regulation of lung protective angiotensin converting enzyme 2, autoimmunity, and genetic factors. It seems that both abnormal immune responses and injury to immune cells may be key factors in the pathogenesis of this new disease.