Neutrophils are an essential component of the innate immune response, but their prolonged activation can lead to chronic inflammation. Consequently, neutrophil homeostasis is tightly regulated through balance between granulopoiesis and clearance of dying cells. The bone marrow is both a site of neutrophil production and the place they return to and die. Myeloproliferative neoplasms (MPN) are clonal hematopoietic disorders characterized by the mutations in three types of molecular markers, with emphasis on Janus kinase 2 gene mutation (JAK2V617F). The MPN bone marrow stem cell niche is a site of chronic inflammation, with commonly increased cells of myeloid lineage, including neutrophils. The MPN neutrophils are characterized by the upregulation of JAK target genes. Additionally, MPN neutrophils display malignant nature, they are in a state of activation, and with deregulated apoptotic machinery. In other words, neutrophils deserve to be placed in the midst of major events in MPN. Our crucial interest in this review is better understanding of how neutrophils die in MPN mirrored by defects in apoptosis and to what possible extent they can contribute to MPN pathophysiology. We tend to expect that reduced neutrophil apoptosis will establish a pathogenic link to chronic inflammation in MPN.

Experimental autoimmune encephalomyelitis (EAE) is characterized by appearance of anti-myelin autoantibodies in the blood and with the increased expression of MHC (major histocompatibility complex) class I and II antigens in the brain tissue. Although there is an evidence of possible linkage between influenza vaccination and development of autoimmune processes, the precise mechanisms of action of this vaccine on EAE-induction is still unclear. In this study, effects of influenza vaccine on clinical sign, antimyelin antibody titer in the blood by ELISA test and expression of MHC class I and II molecules immunohistochemistry were examined in the brain of C57BL mice with EAE. EAE was induced by MOG 35-55 protein in 16 of 32 mice. Influenza split vaccine was administered to eight MOG-induced EAE mice and to eight previously nontreated mice. A significant increase of anti-influenza antibody was detected in vaccinated mice compared to nontreated mice. Also, significant increase of antimyelin antibodies was detected in mice with EAE compared to vaccinated group without EAE and control group, respectively. In EAE-influenza vaccinated mice, a mild but not significant increase of antimyelin antibodies was detected, compared to EAE mice. High expression of MHC-II and mild expression of MHC-I were detected in the brain of mice with EAE. No expressions were detected in vaccinated and normal intact brains. Similar staining was found between EAE-vaccinated and EAE group in both MHC-I and MHC-II expression. The results obtained show that influenza vaccine has no significant influence on EAE induction and severity of autoimmune processes.

Calf bronchopneumonia is complex multifactorial disease and for its accurate diagnosis and therapy, besides clinical examination, microbiologic, hematologic and biochemical analyses could be necessary. In general, additional analyses are not implemented, mainly because the disease biomarkers are not defined. To establish which analysis might be useful for determining the severity of the disease, we analyzed 23 three-month old calves with mild clinical signs of bronchopneumonia and 15 age-matched healthy calves. Pasteurella multocida was isolated from deep nasal swabs of diseased calves. Peripheral blood erythrocyte and leukocyte count of bronchopneumonic and healthy calves showed no difference. Serum proteins, lipoproteins and lipids were analyzed with spectrophotometry, agarose gel electrophoresis, non-reducing SDS-PAGE, gel zymography, and thin-layer chromatography. The bronchopneumonic calves had an increased level of circulating immune complexes and α globulins, which contain some of the positive acute phase proteins. In diseased calves the increased concentration of total γ globulins (IgG), due to an increased concentration of anionic γ globulins (predominately IgG1), was detected. The increased concentration of anionic γ globulins followed by increased concentration of transferrin (negative acute phase protein) and HDL cholesterol, decreased concentration of LDL-cholesterol, unchanged activity of matrix metalloproteases and leukocyte counts might reflect the obvious absence of generalized inflammation. A positive correlation was found between the acquired results and the appearance of mild clinical signs. Therefore, we believe that the parameters analyzed in the peripheral blood could be applied as reliable disease markers to distinguish between severe (inflammatory) and mild forms of calf bronchopneumonia and to predict a better outcome for these calves.

Myelin oligodendrocyte glycoprotein (MOG) is a protein widely used in the induction of experimental autoimmune encephalomyelitis (EAE) for studying human multiple sclerosis (MS). In C57BL/6 female mice aged eight weeks, we administered subcutaneously MOG35-55 peptide in CFA (complete Freund?s adjuvant) along with pertussis vaccine injected intraperitoneally. We observed the sign of flaccid tail as early as thirteen days post-immunization in five of twelve animals. Hematoxylin and eosin staining of paraffin-embedded sections of lymph nodes and spleen revealed the presence of germinal centers in the immunized animals. In the control group of animals, lymphoid follicles without germinal centers were observed. Immunohistochemical staining of spleen sections revealed an expression of MHC II molecules in the EAE-induced group. We would like to point out that even though the clinical signs are mild, the morphological changes are apparent in the lymph nodes and spleen of MOG35-55-immunized mice.

Transforming growth factor beta (TGF-β) plays different roles in health and disease. TGF-β has been assumed as a dual factor in tumor growth, since it can repress epithelial tumor development in early stages, while it acts as a tumor promoter in the late stages of tumor progression. The cancer cells, during cancerogenesis, acquire migration and invasion capacities and finally they metastasize. The urokinase type plasminogen activator (uPA) system, comprised of uPA, the cell surface receptor (uPAR) and plasminogen-plasmin, is involved in the proteolytic degradation of the extracellular matrix and it also regulates several critical cellular events by its capacity to trigger the activation of intracellular signaling pathways. This enables the cancer cell survival, its dissemination, and enhancement of cell malignancy during tumor progression. The expression of both uPA and uPAR is finely regulated in normal development, but their expression is deregulated in cancer. TGF-β regulates uPA expression in cancer cells while uPA, by conversion of plasminogen to active form, plasmin, may release TGF-β from its latent state. Thus, these pathways cross-regulate each other by mutual feedback contributing to tumor progression. Here, we review the specific roles and the interplay between TGF-β and uPA system in cancer cells, the current cancer therapies and the novel patents focused mainly on uPA and TGF-beta ligands and their cell surface receptors respectively. Finally, with regard to the mutual activity of uPA and TGF-β in tumorigenesis, the aim of this review is to expose the potentiality of TGF-β and uPA systems as becoming combinatorial targets for therapies and patents.