The vascular E-selectin binds to the leukocyte integrins CD11/CD18

Leukocyte adhesion involves at least three molecular familiesof adhesion proteins: the leukocyte integrins CD11/CD18, theintercellular adhesion molecules (ICAMs) and the carbohydrate-bindingL-, E- and P-selectins. The intercellular adhesion moleculesare well-known ligands for the CD11/CD18 integrins. We now showthat E-selectin specifically binds to the sialyl Le^x carbohydrateepitopes of leukocyte integrins. Thus, the different familiesof leukocyte adhesion molecules form an integrated adhesionnetwork. adhesion integrins leukocyte selectin     

The More the Merrier: Swarming as an Antipredator Strategy in the Mysid <Emphasis Type="Italic">Neomysis Integer</Emphasis>

The swarming behaviour of a Baltic littoral mysid shrimp, Neomysis integer, was studied both in the presence and absence of a predator (European perch, Perca fluviatilis L.). I performed two kinds of laboratory experiments. First, the swarming tendency of mysids and the effect of swarm size on swarm choice were studied. Second, the ingestion rate of mysids was measured when feeding alone versus in a swarm. The results indicate that N. integer actively join swarms. The avoidance of the perch by N. integer individuals was stronger when there was a swarm present. Larger swarms were preferred over smaller ones regardless of presence or absence of the predator. The overall feeding rate was similar when feeding alone and in swarm, but predator cues reduced feeding rate only when the mysids were feeding alone. This study demonstrates the capability of N. integer to assess predation risk and social context and alter their behaviour accordingly.     

Requirement for RNA helicase CsdA for growth of Yersinia pseudotuberculosis IP32953 at low temperatures

The expression of csdA, encoding an RNA helicase, was induced at 3°C in Yersinia pseudotuberculosis. The role of CsdA in Y. pseudotuberculosis under cold conditions was confirmed by impaired growth of insertional csdA mutants at 3°C. The results suggest that CsdA is crucial for Y. pseudotuberculosis survival in the chilled food chain.     

Production of monocytic cells from bone marrow stem cells: therapeutic usage in Alzheimer's disease

Accumulation of amyloid β (Aβ) is a major hallmark in Alzheimer's disease (AD). Bone marrow derived monocytic cells (BMM) have been shown to reduce Aβ burden in mouse models of AD, alleviating the AD pathology. BMM have been shown to be more efficient phagocytes in AD than the endogenous brain microglia. Because BMM have a natural tendency to infiltrate into the injured area, they could be regarded as optimal candidates for cell-based therapy in AD. In this study, we describe a method to obtain monocytic cells from BM-derived haematopoietic stem cells (HSC). Mouse or human HSC were isolated and differentiated in the presence of macrophage colony stimulating factor (MCSF). The cells were characterized by assessing the expression profile of monocyte markers and cytokine response to inflammatory stimulus. The phagocytic capacity was determined with Aβ uptake assay in vitro and Aβ degradation assay of natively formed Aβ deposits ex vivo and in a transgenic APdE9 mouse model of AD in vivo. HSC were lentivirally transduced with enhanced green fluorescent protein (eGFP) to determine the effect of gene modification on the potential of HSC-derived cells for therapeutic purposes. HSC-derived monocytic cells (HSCM) displayed inflammatory responses comparable to microglia and peripheral monocytes. We also show that HSCM contributed to Aβ reduction and could be genetically modified without compromising their function. These monocytic cells could be obtained from human BM or mobilized peripheral blood HSC, indicating a potential therapeutic relevance for AD.     

Melanoma-Associated Cancer-Testis Antigen 16 (CT16) Regulates the Expression of Apoptotic and Antiapoptotic Genes and Promotes Cell Survival

Cancer-testis (CT) antigens are predominantly expressed in testis or placenta, but absent in most adult tissues. During malignant transformation CT genes are often activated. CT antigen 16 (CT16, PAGE5) is frequently expressed in advanced melanoma but its biological function has been unknown. To examine the role of CT16 in cell survival we knocked it down in A2058 melanoma cells using specific siRNAs and exposed the cells to cancer drug cisplatin known to induce apoptosis. As a result, cell survival was markedly decreased. To study the effects of CT16 on cell survival in more detail, the cellular gene expression profiles were investigated after CT16 silencing in CT16 positive A2058 melanoma cells, as well as after CT16 overexpression in CT16 negative WM-266-4 melanoma cells. Among the 11 genes both upregulated by CT16 silencing and downregulated by CT16 overexpression or vice versa, 4 genes were potentially apoptotic or antiapoptotic genes. CT16 was recognized as a positive regulator of antiapoptotic metallothionein 2A and interleukin 8 genes, whereas it inhibited the expression of apoptosis inducing dickkopf 1 (DKK1) gene. In addition CT16 enhanced the expression of fatty acid binding protein 7, a known promoter of melanoma progression. The effect of CT16 on DKK1 expression was p53 independent. Furthermore, CT16 did not regulate apoptotic genes via DNA methylation. In twenty melanoma metastasis tissue samples average DKK1 mRNA level was shown to be significantly (p<0.05) lower in high CT16 expressing tumors (n = 3) when compared to the tumors with low CT16 expression (n = 17). Thus, our results indicate that CT16 promotes the survival of melanoma cells and is therefore a potential target for future drug development.     

Importance of molecular studies on major blood groups--intercellular adhesion molecule-4, a blood group antigen involved in multiple cellular interactions

Several blood groups, including the LW-blood group were discovered in the first part of last century, but their biochemical characteristics and cellular functions have only more recently been elucidated. The LW-blood group, renamed ICAM-4 (CD242), is red cell specific and belongs to the intercellular adhesion molecule family. ICAM-4 binds to several integrin receptors on blood and endothelial cells and is thus able to form large cellular complexes containing red cells. Its physiological function(s) has remained incompletely understood, but recent work shows that macrophage integrins can bind red cells through this ligand. In this article we discuss molecular properties of major blood group antigens, describe ICAM-4 in more detail, and show that phagocytosis of senescent red cells is in part ICAM-4/beta(2)-integrin dependent.     

Light regulation of CaS, a novel phosphoprotein in the thylakoid membrane of Arabidopsis thaliana

Exposure of Arabidopsis thaliana plants to high levels of light revealed specific phosphorylation of a 40 kDa protein in photosynthetic thylakoid membranes. The protein was identified by MS as extracellular calcium-sensing receptor (CaS), previously reported to be located in the plasma membrane. By confocal laser scanning microscopy and subcellular fractionation, it was demonstrated that CaS localizes to the chloroplasts and is enriched in stroma thylakoids. The phosphorylation level of CaS responded strongly to light intensity. The light-dependent thylakoid protein kinase STN8 is required for CaS phosphorylation. The phosphorylation site was mapped to the stroma-exposed Thr380, located in a motif for interaction with 14-3-3 proteins and proteins with forkhead-associated domains, which suggests the involvement of CaS in stress responses and signaling pathways. The knockout Arabidopsis lines revealed a significant role for CaS in plant growth and development.