Zeitschrift für Immunbiologie

Objective: Multiple myeloma (MM) is a hematologic disease characterized by hyper-proliferation of antibody secreting B-cells. One of the most severe accompanying symptoms in MM is the destruction of bone tissue. Thus, the use of bone morphogenetic proteins (BMPs) for MM treatment seems to be a good option since these proteins are capable to induce formation of bone tissue in vivo and additionally can suppress cell proliferation of malignant Bcells. But, the different BMP family members vary in their biological activities also in terms of donor specific differences of addressed cells. In this study we analyzed signal transduction of two different TGFβ family members, BMP2 and GDF5, in different MM cell lines.
Methods: Ten MM cell lines were stimulated either with BMP2 or GDF5 and cell proliferation was analyzed by WST-1 assays. Receptor expression levels were determined by qRT-PCR for relevant BMP receptors. SMAD-1/5/8 phosphorylation was analyzed by Western blot and correlated to the expression levels of inhibitory (i)-SMADs, SMAD-6 and SMAD-7 proteins, respectively.
Results: Only three out of ten investigated cell lines were BMP2 responsive, one of which was additionally sensitive to GDF5. Depending on the expression of the required receptors the different cell lines could be divided into three subgroups. The first group expressed all receptor chains which are crucial for proper signal transduction and was ligand sensitive, the second also expressed the required receptors, but appeared ligand-resistant. The third subgroup instead missed at least one or more essential receptor rendering these cells also resistant to ligand exposure. Western blot analyses addressing phosphorylated SMAD-1/5/8 proteins revealed that the second group showed no or at least extremely reduced levels of SMAD-1/5/8 phosphorylation levels upon ligand exposure. Furthermore, Western blot analyses also showed that non-responsive cells expressed the inhibitory SMAD-7 protein at high levels prior to ligand stimulation. In contrast, the BMP2 responsive cells did not express SMAD-7 but instead expressed SMAD-6 at high levels prior to ligand stimulation.
Conclusion: Aside of the expression of essential receptors, further factors are decisive for proper BMP signal transduction in MM cells such as the individual expression levels of SMAD-6 and SMAD-7 in unstimulated cells. The conspicuous opposing basal expression levels of either SMAD-6 or SMAD-7 might be used as prediction whether a particular MM cell line appears ligand-responsive or ligand-resistant.

Objective: Secretory granules (SG) and lipid bodies (LB) are the primary organelles that mediate functional responses in mast cells. SG contains histamine and matrix-active proteases, while LB are reservoirs of arachidonic acid and its metabolites, precursors for rapid synthesis of eicosanoids such as LTC4. Both of these compartments can be dynamically or ontologically regulated, with metabolic and immunological stimuli altering lipid body content and granule numbers responding to contextual signals from tissue. We previously described that chronic in vitro or in vivo hyperinsulinemia expands the LB compartment with a concomitant loss of SG capacity, suggesting that this ratio is dynamically regulated. The objective of the current study is to determine if chronic insulin exposure initiates a transcriptional program that biases model mast cells towards a lipogenic state with accompanying loss of secretory granule biogenesis.

Methods: We used a basophilic leukemic cell line with mucosal mast cell-like features as a model system. We tested the hypothesis that chronic insulin exposure initiates a transcriptional program that biases these model mast cells towards a lipogenic state with accompanying loss of secretory granule biogenesis. Transcriptional arrays were used to map gene expression patterns. Biochemical, immunocytochemical and mediator release assays were used to evaluate organelle numbers and functional responses.

Results: In a mucosal mast cell model, the rat basophilic leukemia line RBL2H3, mast cell granularity and SG numbers are inversely correlated with LB numbers. Chronic insulin exposure appears to modulate gene networks involved in both lipid body biogenesis and secretory granule formation. Western blot analysis confirms upregulation of protein levels for LB proteins, and decreases in proteins that are markers for SG cargo.

Conclusions: The levels of insulin in the extracellular milieu may modify the phenotype of mast cell-like cells in vitro.

This analytical review presents the mechanisms used by opportunic pathogenic and obligate pathogenic bacteria to resist human innate immunity pressure. The main mechanisms of innate immune system and bacterial resistance are described. The main focus of this review is on the bacterial proteases involved in the resistance to the immune pressure.

Acute glomerulonephritis caused by Group A beta hemolytic streptococci and other organisms such as staphylococcus and gram negative bacteria is a rare occurrence in pregnancy. It should be considered in differential diagnosis in pregnant lady presenting with body edema, hematuria and reduced urine output.

Heck’s disease, or Focal Epithelial Hyperplasia (FEH), caused by Human Papilloma Virus (HPV) subtypes 13 and mainly 32, is a rare and benign pathology of the oral mucosa; diagnosis is confirmed by PCR analysis.

This is a common disease in the Mayan and other Native-American populations, most frequently between 2-13 years. Risk factors include lower income class, poor hygiene and genetic predisposition.

This cross-sectional study aims to determine the prevalence of clinically compatible lesions of FEH in children from low, middle and high-income in 3 elementary schools in Yucatan, Mexico.

Clinical evaluation was conducted and documented for later analysis by a dermatologist familiar with FEH. Samples were taken and HPV-13 was identified by PCR.

The total of 186 subjects were analyzed from the low-income elementary school, with 41 subjects presenting FEH lesions and 76 presented HPV-13 upon PCR analysis. In the middle-income school, of the 144 subjects studied, 3 had FEH lesions and 8 presented HPV-13 upon PCR analysis. In the high-income elementary school, 96 students were studied, and none presented FEH lesions, however, 6 had HPV-13 positivity.

FEH and HPV-13 prevalence were inversely proportional to socioeconomic status. Lacking an association to a particular gender or difference in the age groups studied.