Biomedical subjects

Wayne Russell

Publications and source records attributed to Wayne Russell.

5 recordsLinked to original sources

PubMed2006

Streptococcal M protein: a multipotent and powerful inducer of inflammation.

Severe infections with Streptococcus pyogenes, an important human pathogen, are associated with massive inflammatory reactions in the human host. Here we show that streptococcal M protein interacts with TLR2 on human peripheral blood monocytes. As a consequence, monocytes express the cytokines IL-6, IL-1beta, and TNF-alpha. This response is significantly increased in the presence of neutrophil-derived heparin-binding protein (HBP), which co-stimulates monocytes by interacting with CD11/CD18. Analysis of tissue biopsies from patients with necrotizing fasciitis revealed recruitment of neutrophils and monocytes to the infectious site, combined with the release of HBP. The results show that M protein, in synergy with HBP, evokes an inflammatory response that may contribute to the profound pathophysiological consequences seen in severe streptococcal infections.

Animals↗

PubMed2004

M protein, a classical bacterial virulence determinant, forms complexes with fibrinogen that induce vascular leakage.

Increased vascular permeability is a key feature of inflammatory conditions. In severe infections, leakage of plasma from the vasculature induces a life-threatening hypotension. Streptococcus pyogenes, a major human bacterial pathogen, causes a toxic shock syndrome (STSS) characterized by excessive plasma leakage and multi-organ failure. Here we find that M protein, released from the streptococcal surface, forms complexes with fibrinogen, which by binding to beta2 integrins of neutrophils, activate these cells. As a result, neutrophils release heparin binding protein, an inflammatory mediator inducing vascular leakage. In mice, injection of M protein or subcutaneous infection with S. pyogenes causes severe pulmonary damage characterized by leakage of plasma and blood cells. These lesions were prevented by treatment with a beta2 integrin antagonist. In addition, M protein/fibrinogen complexes were identified in tissue biopsies from a patient with necrotizing fasciitis and STSS, further underlining the pathogenic significance of such complexes in severe streptococcal infections.

Animals↗

PubMed2004

Resource use and cost of care for patients hospitalised with community acquired pneumonia: impact of adherence to infectious diseases society of america guidelines.

OBJECTIVE: The objective of this study was to compare the inpatient resource use and cost of care for patients hospitalised with community-acquired pneumonia (CAP) who were treated with preferred antibacterial therapy according to the 1998 Infectious Diseases Society of America (IDSA) guidelines with those who were not treated with preferred therapy. METHODS: A multicentre, observational study was conducted in Florida between 1999 and 2000. Hospitalised adult patients (aged > or = 18 years) started on antibacterial therapy for suspected or confirmed CAP were enrolled in the study. Data collected included patient demographic characteristics, pneumonia risk class, resource use (pharmacy, laboratory, radiology, respiratory services, hospital room and board) and economic data. Risk classification according to Fine et al.'s criteria was determined for each patient. Patient's antibacterial therapy was classified as being preferred or non-preferred according to the 1998 IDSA guidelines. Resource utilisation and cost of care were compared between these two groups. RESULTS: Ninety-nine patients were enrolled in the study. The average age was 60.6 years +/- 20.5 years. The percentage of patients in each risk class (according to Fine et al.) were 11.1% in class I, 39.4% in class II, 29.3% in class III, 16.2% in class IV and 4% in class V. The mean cost of hospitalisation per admission (excluding physician cost) was US 3,490 dollars +/- US 3,058 dollars (median US 2,430 dollars) with hospital room/board accounting for the largest percentage (83.7%), followed by laboratory (8.1%), antibacterial (4.6%), radiology (2.6%) and respiratory (0.9%) cost centres [year 2000 values]. The majority of patients (75.8%) received preferred antibacterials according to the IDSA guidelines. The group treated with preferred antibacterials had a shorter mean length of hospital stay (4.5 vs 6.8 days, p = 0.002), a lower total cost of hospitalisation (mean US 3,009 dollars +/- US 2,682 dollars vs US 4,992 dollars +/- US 3,686 dollars; median US 2,047 dollars vs US 3,805 dollars, p = 0.021) and lower antibacterial costs (mean US 117 dollars +/- US 79 dollars vs US 301 dollars +/- US 409 dollars; median US 97 dollars vs US 171 dollars, p = 0.038) compared with patients who did not receive preferred therapy. CONCLUSION: Implementation of protocols according to IDSA guidelines may result in cost savings to institutions wishing to reduce the economic burden associated with treating hospitalised patients for CAP.

Adult↗

PubMed2003

The conversion of fibrinogen to fibrin at the surface of curliated Escherichia coli bacteria leads to the generation of proinflammatory fibrinopeptides.

The inflammatory response to bacterial infection is the result of a complex interplay between bacterial products and host effector systems, such as the immune and complement systems. Here we show that Escherichia coli bacteria expressing fibrous surface proteins, known as curli, assemble and activate factors of the human coagulation cascade at their surface. As a result of this interaction, fibrinogen is converted to fibrin and fibrinogen-derived peptides, termed fibrinopeptides, are generated. The molecular mechanisms behind the bacteria-induced formation of fibrinopeptides were investigated and shown to be triggered by the activation of the contact system, also known as the kallikrein/kinin system or the intrinsic pathway of coagulation. Samples containing fibrinopeptides generated by the interaction between bacteria and plasma were injected into animals and the inflammatory response was monitored. We found that this treatment provoked an infiltration of white blood cells, and the induction of the proinflammatory cytokine MCP-1 at the inflamed site. Our results therefore demonstrate that activation of the coagulation system at the bacterial surface contributes to the pathophysiology of bacterial infectious diseases.

Amino Acid Sequence↗

PubMed2002

Respiratory tract mucins: structure and expression patterns.

Goblet cells produce mainly MUC5AC, but also MUC5B and some MUC2 in apparently 'irritated' airways. MUC5B dominates in the submucosal glands although a little MUC5AC and MUC7 are usually present. MUC4 originates from the ciliated cells. After separation into a gel and a sol phase, lysozyme and lactoferrin are enriched in the salivary gel phase suggesting that mucus may act as a matrix for 'protective' proteins on the mucosal surface. A salivary MUC5B N-terminal fragment consistent with a cleavage event in the D' domain was detected with antibodies against various N-terminal peptide sequences suggesting that assembly of MUC5B occurs through a mechanism similar to that of the von Willebrand factor. Identification of additional cleavage sites C-terminal to the D' domain suggests that most of the N-terminal low-glycosylated part of MUC5B may be removed without affecting the oligomeric nature of the mucin. Possibly, the generation of mucins with different macromolecular properties through proteolytic 'processing' is one way of adapting the mucus polymer matrix to meet local physiological demands. Monomeric mucins that appear to turn over rapidly in the airway epithelium have been identified using radiolabelled mucin precursors. 'Shedding' of such mucins after microbe attachment may prevent colonization of epithelial surfaces.

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