J S Maizes | PubMed Health

PubMed2000

Oxygen transport and utilization.

The evaluation and management of oxygen delivery (Do2) and consumption (Vo2) of patients with acute medical and surgical illnesses have been subject to controversy and reevaluation. It has been established that a relationship between oxygen delivery and oxygen consumption exists, and is very complex, particularly in diseases in which various factors individually or collectively affect it. The care of critically ill patients routinely involves the manipulation of the Vo2-Do2 relationship, and extensive research, both experimental and clinical, has been done to improve our understanding of this relationship in health and disease with the hope for improved outcomes. Regional measures of oxygenation are a relatively new area of interest with a limited amount known about the regional relationship between Do2 and Vo2. The adequacy of regional oxygenation appears to play an important role in organ dysfunction in critical illness. Standard measures of assessing systemic oxygenation are often insensitive in detecting tissue hypoxia, which can often vary among and within various organs. New noninvasive technologies to measure the adequacy of regional measures of oxygenation are being developed, with gastrointestinal tonometry getting much clinical attention. The exact role of these technologies in the management of critically ill patients, and whether they will improve survival, has not yet been determined. It is likely that the ability to care successfully for critically ill patients will come from a better understanding of not only global, but also regional, cellular, and subcellular metabolism.

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PubMed1999

Modulation of immune complex-induced inflammation in vivo by the coordinate expression of activation and inhibitory Fc receptors.

Autoantibodies and immune complexes are major pathogenic factors in autoimmune injury, responsible for initiation of the inflammatory cascade and its resulting tissue damage. This activation results from the interaction of immunoglobulin (Ig)G Fc receptors containing an activation motif (ITAM) with immune complexes (ICs) and cytotoxic autoantibodies which initiates and propagates an inflammatory response. In vitro, this pathway can be interrupted by coligation to FcgammaRIIB, an IgG Fc receptor containing an inhibitory motif (ITIM). In this report, we describe the in vivo consequences of FcgammaRII deficiency in the inflammatory response using a mouse model of IC alveolitis. At subthreshold concentrations of ICs that fail to elicit inflammatory responses in wild-type mice, FcgammaRII-deficient mice developed robust inflammatory responses characterized by increased hemorrhage, edema, and neutrophil infiltration. Bronchoalveolar fluids from FcgammaRII-/- stimulated mice contain higher levels of tumor necrosis factor and chemotactic activity, suggesting that FcgammaRII deficiency lowers the threshold of IC stimulation of resident cells such as the alveolar macrophage. In contrast, complement- and complement receptor-deficient mice develop normal inflammatory responses to suprathreshold levels of ICs, while FcRgamma-/- mice are completely protected from inflammatory injury. An inhibitory role for FcgammaRII on macrophages is demonstrated by analysis of FcgammaRII-/- macrophages which show greater phagocytic and calcium flux responses upon FcgammaRIII engagement. These data reveal contrasting roles for the cellular receptors for IgG on inflammatory cells, providing a regulatory mechanism for setting thresholds for IC sensitivity based on the ratio of ITIM to ITAM FcgammaR expression. Exploiting the FcgammaRII inhibitory pathway could thus provide a new therapeutic approach for modulating antibody-triggered inflammation.

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