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M Protein (m + protein)

Distribution by Scientific Domains

Life Sciences	50%
Medical Sciences	42%

Selected Abstracts

Evasion of macrophage scavenger receptor A-mediated recognition by pathogenic streptococci

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2008
Thomas Areschoug
Abstract PRR recognize conserved structures on pathogenic microbes and are important for the defense against invading microorganisms. However, accumulating evidence indicates that many pathogens have evolved mechanisms to avoid recognition by PRR. One type of PRR is the macrophage scavenger receptor A (SR-A), which has been shown to play an important role in recognition and non-opsonic phagocytosis of pathogenic bacteria. The bacterial ligands for SR-A have been suggested to be LPS or lipoteichoic acid. Here, we use murine bone marrow-derived macrophages to analyze the role of SR-A in non-opsonic phagocytosis of two major Gram-positive pathogens, Streptococcus agalactiae (group B streptococcus; GBS) and Streptococcus pyogenes. We show that the polysaccharide capsule of GBS and the surface M protein of S. pyogenes, two important virulence factors, prevent SR-A-mediated non-opsonic phagocytosis of streptococci. The sialic acid moiety of the GBS capsule was crucial for its ability to prevent recognition by SR-A. Moreover, we show that a ligand on GBS recognized by SR-A in the absence of capsule is the surface lipoprotein Blr. These findings represent the first example of a microbial strategy to prevent recognition by SR-A and suggest that bacterial surface proteins may be of importance as ligands for SR-A. [source]

Peripheral blood mononuclear cells proliferation and Th1/Th2 cytokine production in response to streptococcal M protein in psoriatic patients

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 5 2006
Rolando Pérez-Lorenzo
Background, Psoriasis is a chronic skin disease that is probably a T cell-mediated autoimmune condition which is strongly associated with streptococcal throat infections. Although some groups have associated the involved response with different streptococcal antigens, M protein has been described as the major virulence factor of Streptococcus pyogenes. Thus, it is necessary to describe some features of the cellular responses to this streptococcal antigen. Methods, Proliferation and Th1/Th2 cytokine production of peripheral blood mononuclear cells (PBMC) in response to total soluble extracts from type M5 S. pyogenes with (TSE37Sp) and without (M,TSESp) M protein were analyzed in 10 psoriatic patients and 10 healthy controls. Results, PBMC from both patients and controls proliferated to both extracts. Responses to M,TSESp were significantly lower than those to TSE37Sp (P < 0.05). PBMC IL-2 and ,IFN production after TSE37Sp stimulus was much higher than after M,TSESp antigenic stimulation in both groups (P < 0.05). Meanwhile, IL-4 production was quite low in both groups and in response to both extracts. We found a differential production of IL-10 between groups. PBMC from healthy controls responded to TSE37Sp with a much higher production of this cytokine as compared to the responses showed to M,TSESp while the cells from psoriatic patients responded without differences in the production of IL-10. Conclusion, Results obtained suggest an important Th1 response to M protein in psoriatic patients which could be associated with the cellular responses involved in psoriasis, while healthy subjects respond in a probably non-Th2 IL-10 producing regulatory T cells fashion. [source]

The histological and pathogenetic spectrum of cutaneous disease in monoclonal gammopathies

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 8 2008
Franco Rongioletti
The dermatological disorders associated with monoclonal gammopathies are clinically heterogeneous and may be divided into four groups with distinctive pathogenetic mechanisms (a) specific (infiltrative) disorders including primary and secondary cutaneous plasmacytoma and cutaneous lymphoplasmacytic infiltration of Waldenström's disease (b) skin disorders because of the deposition of monoclonal immunoglobulin (M protein), including amyloidoisis macroglobulinemia cutis, light chain deposition of Randall's disease, follicular spicules of the nose, and cryoglobulinemia (c) skin disorders associated with monoclonal gammopathies, including highly associated (>50%), weakly associated (<50%) or anecdotal and (d) miscellaneous (non specific). In most cases, histopathology is crucial to confirm or to diagnose those skin conditions and is also very useful to understand their pathogenetic mechanisms. [source]

Detection of antibodies against human metapneumovirus by western blot using recombinant nucleocapsid and matrix proteins

JOURNAL OF MEDICAL VIROLOGY, Issue 8 2006
Nobuhisa Ishiguro
Abstract Detection of antibodies against individual proteins of human metapneumovirus (hMPV) is important in the analysis of immune responses to hMPV. Specific antibodies against nucleocapsid (N) and matrix (M) proteins in 97 serum samples were tested by Western blot using recombinant N and M proteins of hMPV expressed in Escherichia coli. The results were compared with those of immunofluorescence assays (IFAs) based on hMPV-infected LLC-MK2 cells, which expressed the whole hMPV proteins. Thirty (61.2%) and 31 (63.3%) of 49 serum samples with titers of >/=1:160 by IFA reacted with N and M proteins, respectively. Only 2 (4.2%) of 11 serum samples with titers of 1:80 by IFA reacted with N and M proteins. Antibodies against N and M proteins were not detected in 37 serum samples with titers of <1:40 by IFA. These results indicate that the antibodies against N and M proteins are highly specific (100%) but less sensitive (42.1%, N protein; 40.8%, M protein) than those against whole proteins of hMPV detected by IFA. The reactivity of sera with the recombinant N protein and that with the recombinant M protein correlated well (correlation coefficient of 0.79), and the concordance of reactivities was 91% (,,=,0.79). In summary, both recombinant N and M proteins of hMPV were antigenic, and the responses to N and M protein varied among patients. Therefore, Western blot using N and M proteins provide a useful tool for analysis of immune responses to hMPV. J. Med. Virol. 78:1091,1095, 2006. © 2006 Wiley-Liss, Inc. [source]

Domains of group A streptococcal M protein that confer resistance to phagocytosis, opsonization and protection: implications for vaccine development

MOLECULAR MICROBIOLOGY, Issue 1 2006
Jason D. McArthur
Summary Streptococcus pyogenes (group A streptococcus) colonizes skin and throat tissues resulting in a range of benign and serious human diseases. Opsonization and phagocytosis are important defence mechanisms employed by the host to destroy group A streptococci. Antisera against the cell-surface M protein, of which over 150 different types have been identified, are opsonic and contribute to disease protection. In this issue of Molecular Microbiology, Sandin and colleagues have comprehensively analysed the regions of M5 protein that contribute to phagocytosis resistance and opsonization. Human plasma proteins bound to M5 protein B- and C-repeats were shown to block opsonization, an observation that needs to be carefully considered for the development of M protein-derived vaccines. While safe and efficacious human group A streptococcal vaccines are not commercially available, candidate M protein-derived vaccines have shown promise in murine vaccine models and a recent phase 1 human clinical trial. [source]

Role of group A Streptococcus HtrA in the maturation of SpeB protease

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 24 2007
Jason N. Cole
Abstract The serine protease high-temperature requirement A (HtrA) (DegP) of the human pathogen Streptococcus pyogenes (group A Streptococcus; GAS) is localized to the ExPortal secretory microdomain and is reportedly essential for the maturation of cysteine protease streptococcal pyrogenic exotoxin B (SpeB). Here, we utilize HSC5 (M5 serotype) and the in-frame isogenic mutant HSC5,htrA to determine whether HtrA contributes to the maturation of other GAS virulence determinants. Mutanolysin cell wall extracts and secreted proteins were arrayed by 2-DE and identified by MALDI-TOF PMF analysis. HSC5,htrA had elevated levels of cell wall-associated M protein, whilst the supernatant had higher concentrations of M protein fragments and a reduced amount of mature SpeB protease, compared to wild-type (WT). Western blot analysis and protease assays revealed a delay in the maturation of SpeB in the HSC5,htrA supernatant. HtrA was unable to directly process SpeB zymogen (proSpeB) to the active form in vitro. We therefore conclude that HtrA plays an indirect role in the maturation of cysteine protease SpeB. [source]

Upregulation of Oncostatin M in Allergic Rhinitis

THE LARYNGOSCOPE, Issue 12 2005
Hee Joon Kang MD
Abstract Objectives: Oncostatin M is a multifunctional cytokine belonging to the interleukin-6 family of cytokines. It has been implicated as an important modulator of lower airway remodeling in the setting of asthma. However, there have been few studies regarding a similar role for the upper airway epithelium in the setting of allergic rhinitis. This study was undertaken to investigate the expression of oncostatin M mRNA and protein in normal and allergic rhinitis nasal mucosa and to localize the expression of the oncostatin M protein in allergic rhinitis. Materials and Methods: Inferior turbinate mucosa samples from 20 patients with perennial allergic rhinitis and 20 matched normal control subjects were obtained. Oncostatin M mRNA was extracted from the inferior turbinate mucosae, then reverse transcriptase-polymerase chain reaction was performed and analyzed semiquantitatively. Differences in expression levels of oncostatin M protein between samples from allergic rhinitis patients and normal control subjects were analyzed through Western blot, and oncostatin M protein was localized immunohistochemically. Results: The expression levels of oncostatin M mRNA and protein were significantly upregulated in patients with allergic rhinitis mucosa. Oncostatin M protein was predominantly localized in the surface epithelium, infiltrating inflammatory cells, vascular endothelium, and submucosal glands and was more strongly expressed in the nasal mucosa of patients with allergic rhinitis than in normal control subjects. Conclusions: Oncostatin M is expressed in the human nasal mucosa and is upregulated in the setting of allergic nasal inflammation. These results suggest a possible contribution of oncostatin M in the remodeling of the nasal mucosa in allergic rhinitis. [source]

Persistence of myeloma protein for more than one year after radiotherapy is an adverse prognostic factor in solitary plasmacytoma of bone

CANCER, Issue 5 2002
Richard B. Wilder M.D.
Abstract BACKGROUND Prognostic factors for solitary plasmacytoma of bone (SPB), whether measured before or after radiotherapy (RT), have not been established. The authors analyzed multiple factors for myeloma-free survival (MFS) and cause-specific survival (CSS) in SPB patients treated with RT alone. METHODS Between 1965 and 2000, 60 patients with carefully staged SPB were treated with RT alone at the M. D. Anderson Cancer Center. Patient ages ranged from 29,77 years (median, 54 years), and 75% of patients had a myeloma (M) protein in the blood and/or urine. No patients showed other lesions on skeletal survey or, in recent years, magnetic resonance imaging (MRI) of the spine; marrow aspirate was normal in all patients. Radiotherapy to the solitary lesion was given to a total dose of 30,70 Gy (median, 46 Gy). The authors analyzed the impact of multiple factors on MFS and CSS, including resolution v. persistence of M protein after RT, secretory v. nonsecretory disease at diagnosis, presence v. absence of an associated soft tissue mass on computed tomography or MRI scan, magnitude of serum M protein elevation at diagnosis, age, spinal v. nonspinal location, Karnofsky performance status, total RT dose, and tumor size. RESULTS Median follow-up was 7.8 years (range, 1.0,25.5 years). On multivariate analysis, persistence of M protein more than one year after RT was the only independent adverse prognostic factor for MFS (P = 0.005) and CSS (P = 0.04). Most patients with M protein that persisted for more than one year after RT were diagnosed with multiple myeloma within 2.2 years of treatment. CONCLUSIONS Patients with M protein that persists for more than one year after RT should be monitored frequently and considered for standard chemotherapy followed by intensive consolidation therapy when they either develop symptoms or show an increasing M protein level. Cancer 2002;94:1532,7. © 2002 American Cancer Society. DOI 10.1002/cncr.10366 [source]

Measles virus nucleocapsid transport to the plasma membrane requires stable expression and surface accumulation of the viral matrix protein

CELLULAR MICROBIOLOGY, Issue 5 2007
Nicole Runkler
Summary In measles virus (MV)-infected cells the matrix (M) protein plays a key role in virus assembly and budding processes at the plasma membrane because it mediates the contact between the viral surface glycoproteins and the nucleocapsids. By exchanging valine 101, a highly conserved residue among all paramyxoviral M proteins, we generated a recombinant MV (rMV) from cloned cDNA encoding for a M protein with an increased intracellular turnover. The mutant rMV was barely released from the infected cells. This assembly defect was not due to a defective M binding to other matrix- or nucleoproteins, but could rather be assigned to a reduced ability to associate with cellular membranes, and more importantly, to a defective accumulation at the plasma membrane which was accompanied by the deficient transport of nucleocapsids to the cell surface. Thus, we show for the first time that M stability and accumulation at intracellular membranes is a prerequisite for M and nucleocapsid co-transport to the plasma membrane and for subsequent virus assembly and budding processes. [source]