REGULATION OF CHEMOKINE RECEPTOR EXPRESSION DURING SEPSIS

Feinstein Institute For Medical Research, Manhasset NY

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our long-range goal is to overcome mechanisms that subvert effective pulmonary defense in septic patients, thereby improving clinical outcome. The objective of this protocol is to assess whether beta chemokine receptor expression is suppressed in circulating macrophages isolated from septic patients, and if so, to evaluate whether the magnitude of this defect correlates with (1) the type of infection (e.g. gram-negative versus gram-positive)or (2) with increased susceptibility to secondary lung infection. The central hypothesis, formulated on the basis of strong in vitro data, is that in septic patients the systemic release of bacterial products, including lipopolysaccahride, triggers a sustained loss of a class of beta chemokine receptors from the surface of macrophages, leaving these cells essentially anergic to beta chemokine signals. The rationale that underlies the proposed research is that the identification of a link between dysregulated beta chemokine receptor responses and adverse outcomes in septic patients would provide us with a previously unrecognized target for therapeutic intervention.