Receptor (SLAM [CD150]) recognition and the V protein sustain swift lymphocyte-based invasion of mucosal tissue and lymphatic organs by a morbillivirus

Experimental infections of ferrets with canine distemper virus (CDV) recapitulate many hallmarks of measles: rash, high fever, viremia, depression of delayed-type hypersensitivity responses, lowered leukocyte counts, and reduced lymphocyte proliferation activity. To understand how a morbillivirus invades the host and causes immunosuppression, we generated CDV either unable to recognize one of the receptors or incapable of expressing either one or both of the candidate interferon antagonist proteins V and C. Variants of these viruses expressing green fluorescent protein were also generated. Striking similarities between CDV infection of ferrets and human immunodeficiency virus host invasion were documented: first, massive early replication in the gut-associated lymphatic tissue, including intestinal Peyer's patches, followed by extensive infection of lymphatic organs, including thymus and circulating lymphocytes. Moreover, T cells were selectively depleted. Thus, CDV takes advantage of mucosal surfaces for host invasion and lymphocytes for swift dissemination. A CDV unable to recognize the signaling lymphocytic activation molecule (SLAM [CD150]) that is expressed in lymphocytes and other immune cells did not spread. A V-defective CDV multiplied with reduced efficiency in lymphocytes and did not inhibit the interferon and cytokine responses. Protein C affected the severity of rash and digestive symptoms elicited by V-defective CDV, but it was dispensable for the invasion of the lymphatic organs. These findings prove formally that SLAM recognition is necessary for morbillivirus virulence. They also reveal how two viral proteins affect pathogenesis: V sustains the swift lymphocyte-based invasion of mucosal tissue and lymphatic organs, whereas C sustains subsequent infection phases.     

Insight of nitric oxide signaling: A potential biomarker with multifaceted complex mechanism in colorectal carcinogenesis

Colorectal carcinogenesis (CRC) is the most important health concerns throughout the World as the tumour cells rapidly spread and abruptly grow in colon and rectum to further organs. Several etiological factors are associated with colorectal carcinogenesis. During invasion and proliferation of tumour cells, various mechanistic molecular pathways are involved in the cells. Nitric Oxide pathway (NO) is one of the important cellular mechanisms associated with tumour cells initiation, invasion and progression. Epidemiological evidences suggest that NO has potential role in development of cancer. The multidisciplinary action of NO on the initiation of cancer depends on several factors including cell type, metastasis stage, and organs involved. This review emphasizes the biological significance of NO in each step of cancer metastasis, its controversial effects for carcinogenesis including initiation, invasion and progression.     

Immune effect of heat-killed multistrain of Lactobacillus acidophilus against Salmonella typhimurium invasion to mice

AIMS: This study attempted to determine whether lactic acid bacteria (LAB) could have a better probiotic function when used as a multistrain mixture, i.e. Mix-LAB, than when used as a monostrain. To this end, three strains of Lactobacillus acidophilus, specifically strain LAP5, LAF1 and LAH7, were heat-killed and mixed. This heat-killed Mix-LAB was used to evaluate the effectiveness of multistrain in inhibiting Salmonella invasion into cultured cells and into organs (spleen and liver) of live mice. METHODS AND RESULTS: BALB/c mice were orally administered with heat-killed Mix-LAB or sterile normal saline (control) for seven consecutive days and then challenged with orally administered Salmonella typhimurium on day 8. Results showed that, at day 6 after the challenge, the mice which had received Mix-LAB exhibited lower rates (P < 0.05) of Salmonella invasion into liver and spleen than did the control mice. Also, before the Salmonella challenge, the serum tumour necrosis factor-alpha (TNF-alpha) levels were not significantly different (P > 0.05) between these two groups of mice. After the challenge, however, the serum TNF-alpha level was significantly elevated (P < 0.05) in the control group, but not significantly changed in the Mix-LAB fed mice. To investigate possible factors involved in heat-killed Mix-LABs antagonistic effect on Salmonella invasion of mouse organs, heat-killed single strain and Mix-LAB were evaluated for ability to inhibit Salmonella invasion into cultured human intestinal Int-407 and Caco-2 cells. Results showed that none of the heat-killed strains were able to protect these cultured cells from Salmonella invasion, even though strains of LAP5 and Mix-LAB were adherent to them. However, study of the activation of murine macrophage Raw 264.7 cells showed that heat-killed Mix-LAB stimulated TNF-alpha production, nitric oxide release, and increased phagocytic activity in macrophages. CONCLUSIONS: Our findings suggest that heat-killed Mix-LAB can inhibit Salmonella invasion of mouse organs through the immunomodulating role of activated macrophage. SIGNIFICANCE AND IMPACT OF THE STUDY: The ability of heat-killed Mix-LAB to prevent bacterial infection in mice was found to be more significant than that of viable monostrain. This effect may be due to the activation of the immune system rather than to the adherence of LAB to the intestine epithelium.     

A large panel of chicken cells are invaded in vivo by Salmonella Typhimurium even when depleted of all known invasion factors

Poultry are the main source of human infection by Salmonella. As infected poultry are asymptomatic, identifying infected poultry farms is difficult, thus controlling animal infections is of primary importance. As cell tropism is known to govern disease, our aim was therefore to identify infected host–cell types in the organs of chicks known to be involved in Salmonella infection and investigate the role of the three known invasion factors in this process (T3SS-1, Rck and PagN). Chicks were inoculated with wild-type or isogenic fluorescent Salmonella Typhimurium mutants via the intracoelomic route. Our results show that liver, spleen, gall bladder and aortic vessels could be foci of infection, and that phagocytic and non-phagocytic cells, including immune, epithelial and endothelial cells, are invaded in vivo in each organ. Moreover, a mutant defective for the T3SS-1, Rck and PagN remained able to colonize organs like the wild-type strain and invaded non-phagocytic cells in each organ studied. As the infection of the gall bladder had not previously been described in chicks, invasion of gall bladder cells was confirmed by immunohistochemistry and infection was shown to last several weeks after inoculation. Altogether, for the first time these findings provide insights into cell tropism of Salmonella in relevant organs involved in Salmonella infection in chicks and also demonstrate that the known invasion factors are not required for entry into these cell types.     

E- and P-Selectins Are Essential for Repopulation of Chronic Myelogenous and Chronic Eosinophilic Leukemias in a Scid Mouse Xenograft Model

In chronic myelogenous (CML) and chronic eosinophilic leukemia (CEL), neoplastic cells spread via the circulation into various extramedullary organs. As E- and P-selectin constitute the starting point for the leucocyte adhesion/invasion cascade, and CEL and CML cells share many properties with normal granulocytes, we investigated the role of these selectins in CEL and CML cell expansion and organ invasion in a xenotransplantation model using scid mice. Using two human leukemic cell lines (EOL-1 and K562), we were able to show that E- and P-selectins mediate leukemia cell tethering and adherence in a laminar flow assay. While E-selectin binding depended on sialylated carbohydrate moieties, P-selectin binding was completely (K562) or partially (EOL-1) independent of these carbohydrates indicating the involvement of non-canonical selectin ligands. In a xenograft model in scid mice, both cell lines invaded the bone marrow and other organs, formed chloromas, and ultimately produced an overt leukemia. In contrast, in E- and P-selectin knockout scid mice, the cells failed to show engraftment in 8 out of 10 animals and even if they did engraft, they produced only little organ invasion and chloroma formation. Together, these data suggest that E- and P-selectins play an important role in leukemic dissemination in CML and CEL.     

Contribution of flagella and invasion proteins to pathogenesis of Salmonella enterica serovar enteritidis in chicks

To explore the relative contribution that flagella and Salmonella invasion proteins make to the virulence of Salmonella enteritidis in poultry, 20-day-old chicks were challenged orally and by subcutaneous injection with wild-type strain SE-HCD, two non-flagellated mutants (fliC::Tn10 mutant and flhD::Tn10 mutant) and two Salmonella invasion protein insertion mutants (sipD and iacP). When injected subcutaneously, wild-type SE-HCD was the only strain to cause substantial mortality and morbidity and to grow well in organs. The flhD mutant of SE-HCD was invasive when given orally, whereas wild-type SE-HCD and the fliC mutant were significantly attenuated. Salmonella invasion protein mutants were not invasive by either route. These results suggest that temporary suppression of Class I regulators of flagellin biosynthesis may aid oral infection in poultry.     

Observations on the histopathology and probable progression of the disease caused by Trichomaris invadens,an invasive ascomycete,in the Tanner crab,Chionoecetes bairdi

Fifty-three Tanner crabs with varying degrees of surface encrustations and internal invasion by Trichomaris invadens were necropsied, processed, and examined to determine the extent of internal tissue invasion and histopathological effects of the infection. Sufficient data were accumulated to provide some insight on the progression, but not the rate, of tissue invasion. The epidermis and subepidermal layers are invaded and virtually replaced by proliferating hyphae. The invasion then proceeds internally, predominantly via the connective tissue. Major muscles and blood vessels are invaded, then invasion of deeper organs, including the hemopoietic tissue, gastrointestinal tract wall, and wall of the heart follows. The eyestalk is infected, usually early in the disease, and the invasion follows a similar pattern to that in the cephalothorax. Massive invasion and destruction of the retina is the major pathological effect. The gill may also be involved, with destruction of the lamellar tissues and invasion and destruction of podocytes in the stem of the gill.     

Protective effects of antibody against intestinal invasion by Escherichia coli

Seven Escherichia coli isolates from newborn calves with diarrhea were examined for enteropathogenic properties. One isolate penetrated into HeLa cells, four produced enterotoxin(s) and the remaining two possessed neither of these properties. Penetration of E. coli into HeLa cells was inhibited by antibody in bovine colostrum and in bovine and rabbit immune sera. The effective antibodies appeared to be mostly of the IgM class. The invasion by E. coli isolates was also examined by inoculation of the bacteria into the small intestine of E. coli-immunized and non-immunized guinea pigs. The isolate which penetrated into HeLa cells could penetrate the intestinal mucosa to be disseminated into various organs of non-immunized guinea pigs, but not of immunized guinea pigs, whereas no other isolates showed such pathogenicity in vivo. The inhibition of the invasion was observed when non-immunized guinea pigs were inoculated with the bacteria together with colostral or serum antibody. The results show the importance of antibody in the local defense mechanism against E. coli invasion.     

Mycoplasma gallisepticum: Influence of cell invasiveness on the outcome of experimental infection in chickens

Recently we have shown that a low (R(low)) and a high laboratory passage (R(high)) of the poultry pathogen Mycoplasma gallisepticum prototype strain R differ markedly in their capability to invade non-phagocytic eukaryotic cells. In the present study the infection traits of these two mycoplasma passages were compared in an in vivo setting. After aerosol inoculation of chickens, M. gallisepticum was re-isolated from the inner organs of birds infected with R(low), whereas no mycoplasma was recovered from the inner organs of birds infected with R(high). These results indicate that the two mycoplasma populations derived from strain R differ in their capacity to cross the mucosal barrier and suggest that cell invasion may play a major role in the observed systemic spreading of M. gallisepticum in its chicken host.     

不同供氮水平下反枝苋的化感作用与资源竞争能力

为探讨反枝苋(Amaranthus retroflexus)在入侵农田生态系统过程中的化感作用与资源竞争能力之间的关系,采用添加活性炭的方法,比较了在有无活性炭条件下,反枝苋与大豆(Glycine max)的生物量积累、生物量分配及不同器官含氮量随供氮水平的变化情况。结果表明,在低供氮水平时,化感作用在竞争中占有的比重较大,在高供氮水平时,化感作用所占的比重相对降低;在高供氮条件下,反枝苋增加了对根和叶的生物量分配,而在低供氮条件下,则增加对繁殖器官的生物量分配;在氮素营养贫瘠的条件下,添加活性炭的大豆含氮量要明显小于不添加活性炭时,随着供氮水平的上升,差异逐渐减小。说明在入侵过程中,反枝苋可以通过调节自身的化感作用和生物量分配来适应不同的氮素营养条件。     

Distribution and variable expression of secretory pathway protein reticulocalbin in normal human organs and non-neoplastic pathological conditions.

Reticulocalbin (RCN) is one member of the Ca(2+)-binding proteins in the secretory pathway and is localized in the endoplasmic reticulum. RCN may play a role in the normal behavior and life of cells, although its detailed role remains unknown. Overexpression of RCN may also play a role in tumorigenesis, tumor invasion, and drug resistance. The new antibody for human RCN is used in the distribution of RCN in normal human organs of fetuses and adults with or without inflammation. Immunohistochemical examination demonstrated a broad distribution of RCN in various organs of fetuses and adults, predominantly in the endocrine and exocrine organs. However, RCN expression was heterogeneous in each constituent cell of some organs. Among non-epithelial organs, vascular endothelial cells, testicular germ cells, neurons, and follicular dendritic cells showed strong staining. Plasma cells were the only RCN-positive cells among hematopoietic and lymphoid cells. In inflammatory conditions, RCN expression was enhanced in both epithelial and non-epithelial cells. Heterogeneous expression of RCN indicates that the amount of RCN needed for cell behavior and life may be variable, depending on each cell type and, therefore, RCN may be helpful in establishing the cell origin of neoplasms in some organs. However, further study is needed to establish the significance of RCN in tumorigenesis and in some peculiar features of neoplasms.     

Histopathology of experimental systemic candidosis in guinea-pigs

Unpretreated Albino guinea-pigs were infected intravenously with Candida albicans. Cutaneous candidosis with (pseudo-) hyphal outgrowth in the hair shafts and in the keratinized layers of the epidermis developed as a consequence of systemic dissemination. The spread of the infection was followed by cultures and by gross- and micropathological study of various organs of different animals during a follow-up period of 35 days. The possible relationship of organ invasion by C. albicans and skin candidosis is discussed.     

Molecular mechanisms exploited by Listeria monocytogenes during host cell invasion

The facultative intracellular bacterial pathogen Listeria monocytogenes has evolved multiple strategies to invade a large panel of mammalian cells. Host cell invasion is critical for several stages of listeriosis pathology such as the initial crossing of the host intestinal barrier and the successive colonization of diverse target organs including the placenta. In this review, we address the main molecular mechanisms known to be used by L. monocytogenes during invasion of nonphagocytic cells and host tissues.     

Monitoring of lung tumour cell growth in artificial membranes

Morbidity of many tumour types is associated with invasion of tumour cells through the basement membrane and subsequent metastasis to vital organs. Tumour invasion is frequently detected late on as many patients present with advanced disease. The method of detecting invasion is through conventional histological staining techniques, which are time consuming and require processing of the sample. This can affect interpretation of the results. In this study, a new imaging technique, optical coherence tomography (OCT), was used to monitor lung tumour cell growth in two artificial membranes composed of either collagen type I or Matrigel. In parallel, standard histological section analysis was performed to validate the accuracy of the monitoring by OCT. Cross-sectional images from OCT revealed that lung tumour cells infiltrated only when low cell seeding density (5 x 10(5)) and low collagen concentration (1.5 mg/ml) were combined. The cells could be easily differentiated from the artificial membranes and appeared as either a brighter layer on the top of the membrane or brighter foci embedded within the darker membrane. These cell-membrane morphologies matched remarkably to the standard histological section images. Our results suggest that OCT has a great potential to become a useful tool for fast and robust imaging of cell growth in vivo and as a potential assessment of cell invasion.     

不同入侵程度紫茎泽兰碳氮磷生态化学计量特征研究

紫茎泽兰(Ageratina adenophora)是一种生态危害性较大的入侵植物。为探讨不同入侵程度下紫茎泽兰的化学计量特征,进一步揭示其营养策略与入侵机制,该研究以紫茎泽兰及其本土伴生种条叶猪屎豆(Crotalaria linifolia)为对象,测定研究了轻度入侵、中度入侵和重度入侵下紫茎泽兰根、茎、叶中碳(C)、氮(N)、磷(P)化学计量特征与其入侵地土壤养分状况,并进一步比较了紫茎泽兰和条叶猪屎豆的C、N、P化学计量特征。结果表明：(1)3种入侵程度下,紫茎泽兰叶N、P含量均显著大于根和茎N、P含量,将更多的N和P分配至叶,增加资源获取,以利快速生长。(2)3种入侵程度下,紫茎泽兰茎N∶P<根N∶P<叶N∶P,且茎N∶P在中度入侵下显著大于轻度入侵,在入侵过程中其茎呈现出较高的生长速率,可促进其获取更多环境资源,增强生长竞争优势。(3)与本土种条叶猪屎豆相比,紫茎泽兰具有更高的根P、茎P含量,根和茎C∶P、N∶P均显著小于条叶猪屎豆,各器官C∶N均显著大于条叶猪屎豆,显示出较高的养分利用效率及较低的资源需求量。(4)紫茎泽兰茎C和叶C、茎N和叶N均呈显著正相关,茎...     

The Siberian tree frog (<Emphasis Type="Italic">Rana amurensis</Emphasis> Bulenger, 1886) in Yakutia

The paper studies the distribution, life style, propagation, nutrition, helminthes invasion, seasonal fluctuations of hematologic parameters, content of ascorbic acid in the organs and glycogen in the liver of the Siberian tree frog.     

CXCR4 promotes oral squamous cell carcinoma migration and invasion through inducing expression of MMP-9 and MMP-13 via the ERK signaling pathway

The increased migration and invasion of oral squamous cell carcinoma cells are key events in the development of metastasis to the lymph nodes and distant organs. Although the chemokine receptor CXCR4 and its ligand, stromal cell-derived factor-1α, have been found to play an important role in tumor invasion, its precise role and potential underlying mechanisms remain largely unknown. In this study, we showed that knockdown of CXCR4 significantly decreased Tca8113 cells migration and invasion, accompanied with the reduction of MMP-9 and MMP-13 expression. Inhibition of ligand binding to CXCR4 by a specific antagonist TN14003, also led to reduced cancer cell migration and invasion. Because the degradation of the extracellular matrix and the basement membrane by proteases, such as matrix metalloproteinases (MMP) is critical for migration and invasion of cancer cells, we investigated the expression of several MMPs and found that the expression of functional MMP-9 and MMP-13 was selectively decreased in CXCR4 knockdown cells. More importantly, decreased cell migration and invasion of CXCR4 knockdown cells were completely rescued by exogenous expression of MMP-9 or MMP-13, indicating that the two MMPs are downstream targets of CXCR4-mediated signaling. Furthermore, we found the level of phosphorylated extracellular signal-regulated kinase (ERK) was significantly decreased in CXCR4-silenced cells, suggesting that ERK may be a potential mediator of CXCR4-regulated MMP-9 and MMP-13 expression in Tca8113 cells. Taken together, our results strongly suggest the underlying mechanism of CXCR4 promoting Tca8113 migration and invasion by regulating MMP-9 and MMP-13 expression perhaps via activation of the ERK signaling pathway.     

Combined effect of environmental temperature and trematodes on fatty acids composition of lipids of Littorina saxatilis (Olivi 1792) (Gastropoda, Prosobranchia)

An effect of environmental temperatures and invasion by helminthes larvae on fatty acids composition of digestive gland lipids of marine littoral gastropod Littorina saxatilis from White Sea and Barents Sea was investigated. We have compared gastropods from boreal and subarctic populations. It was found that gastropods from waters of lower temperature have increased omega3/omega6 fatty acids ratio. However, saturation index of individual membrane phospholipids was not affected. Also, content of eicosenoic acid (20:1) in individual phospholipids was not affected by temperature. Invasion increases the omega3/omega6 ratio of common lipids but not the omega3/omega6 ratio of common and individual phospholipids with the exception of phosphatidilcholine of cold water mollusks from Barents Sea that had this ratio doubled. In contrast to temperature, invasion affects the content of eicosenoic acid that was increased in the investigated organs. Adaptability of these effects is discussed regarding parasite-host system.