Biomedical subjects

Maki Hodnett

Publications and source records attributed to Maki Hodnett.

3 recordsLinked to original sources

PubMed2006

Integrin alphavbeta5 regulates lung vascular permeability and pulmonary endothelial barrier function.

Increased lung vascular permeability is an important contributor to respiratory failure in acute lung injury (ALI). We found that a function-blocking antibody against the integrin alphavbeta5 prevented development of lung vascular permeability in two different models of ALI: ischemia-reperfusion in rats (mediated by vascular endothelial growth factor [VEGF]) and ventilation-induced lung injury (VILI) in mice (mediated, at least in part, by transforming growth factor-beta [TGF-beta]). Knockout mice homozygous for a null mutation of the integrin beta5 subunit were also protected from lung vascular permeability in VILI. In pulmonary endothelial cells, both the genetic absence and blocking of alphavbeta5 prevented increases in monolayer permeability induced by VEGF, TGF-beta, and thrombin. Furthermore, actin stress fiber formation induced by each of these agonists was attenuated by blocking alphavbeta5, suggesting that alphavbeta5 regulates induced pulmonary endothelial permeability by facilitating interactions with the actin cytoskeleton. These results identify integrin alphavbeta5 as a central regulator of increased pulmonary vascular permeability and a potentially attractive therapeutic target in ALI.

Amides↗

PubMed2005

Serum levels of Hsp60 correlate with the development of acute lung injury after trauma.

BACKGROUND: Previous studies have shown that heat shock protein 60 (Hsp60) is a danger signal for the immune system and appears to be a key endogenous inflammatory mediator that activates the toll-like receptors and causes the release of proinflammatory cytokines and nitric oxide by immune competent cells, but no data are available for trauma patients. The purpose of this study was to determine whether Hsp60 could be detected in the serum of patients early after severe trauma and whether its serum level might correlate with the development of acute lung injury (ALI) in trauma patients. METHODS: Clinical data were collected prospectively during a 12-month period for trauma patients who were ventilated mechanically for more than 24 h and who met the following inclusion criteria: Injury Severity Score > or =16, age >18 years. Physiological data for quantitative assessment of organ dysfunction were collected for each patient. Hsp60 levels were measured in the serum of trauma patients. RESULTS: Sixty-four patients with severe trauma were enrolled in the study. Eighteen patients developed ALI (28%). Trauma patients who later developed ALI had significantly higher serum values of Hsp60 than those who did not (4.21 +/- 2.24 ng/mL versus 0.73 +/- 0.26 ng/mL, P < 0.05, mean +/- SE). Furthermore, immature but not mature recombinant Hsp60 induced in vitro the release of nitric oxide (NO) from RAW 264.7 murine macrophages. CONCLUSION: Serum levels of Hsp60 detected within 30 min after trauma correlate with the development of ALI. Immature but mature Hsp60 causes in vitro the release of NO by macrophages, suggesting that the extracellular release of the immature Hsp60 associated with traumatic cell necrosis could be involved in the release of NO by immune competent cells, leading to an activation of the inflammatory response within the lung or other organs.

Adult↗

PubMed2004

In vivo stress preconditioning.

The heat shock or stress protein response is a highly conserved defense mechanism. Activation of the stress protein response by mild hyperthermia or by pharmacological agents allows cells to withstand a subsequent metabolic insult that would otherwise be lethal, a phenomenon referred as "thermotolerance" or "preconditioning." Heat shock response is characterized by increased expression of stress proteins that provide cellular protection, e.g., via increased chaperoning activity in all organisms, from bacteria to animals and humans. Indeed, there is experimental evidence that overexpression of specific heat shock proteins or heat shock factors produce protective effects similar to those observed after stress preconditioning. The purpose of this review is first to discuss the methods used to induce in vivo thermotolerance with mild hyperthermia or pharmacological agents. Then, as an example of the organ protection provided by in vivo stress preconditioning, the second part of this paper will examine how the induction of thermotolerance modulates the lung inflammatory response associated with acute lung injury, thus providing broad organ and tissue protection against oxidative stress associated this syndrome.

Animal Experimentation↗