Immune-cell Membrane Trafficking

Trauma and Sepsis Induced Changes in Immune-cell Membrane Receptor Trafficking

Organ failure following trauma is a leading cause of morbidity and mortality. It appears that the development of organ failure is a direct result of an altered immune response. This altered response results in the production of circulating factors in the blood that causes direct injury to the injured patients' organs. The mechanism in which this altered immune response occurs is unknown. Based on work we have performed in our laboratory, we believe that this response is initiated on the cell membrane of particular immune cells known as macrophages. Although the cell membrane may appear uniform, it is not. The membrane is composed of specific segments that allow proteins to associate with each other forming receptors that are required for immune cell activation. These specific membrane components are composed of various lipids and cholesterol, and have been termed lipid rafts. Based on our laboratory work it appears that these lipid rafts can be altered following injury. In particular both the lipid and protein content within these raft segments may be altered allowing immune cells to become active leading to the production of factors that directly injure normal cells and organs. Thus, we plan to examine if these laboratory findings can be seen in patients suffering from trauma who develop clinical organ failure at Harborview Medical Center. If this is accomplished, this data will lead to the development of both prognostic and therapeutic interventions for the optimal care of injured patient

Study Overview

• Status: Completed
• Conditions: Severe Trauma

• Study Type: Observational
• Enrollment (Actual): 213

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Inclusion criteria:

Description

Inclusion Criteria:

• age 18 years or older, blunt or penetrating trauma and
• one or more of the following: systolic blood pressure less than 90 mmHg at the scene or within one hour of arrival to the Emergency Department, 2) base deficit ≥ -6 within one hour of admission, 3) ISS greater than 25, or 4) more than 6 units of blood transfused in the first 12 hours.-

Exclusion Criteria:

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Assessment of protein and lipid changes in immune cells following severe injury	5/08 to 8/12

Secondary Outcome Measures

Outcome Measure	Time Frame
Assessment of severe injury effect on plasma and cellular lipid content	5/08 to 8/12

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Joseph Cuschieri, MD, University of Washington

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: March 12, 2008
• First Submitted That Met QC Criteria: March 18, 2008
• First Posted (Estimate): March 19, 2008

Study Record Updates

• Last Update Posted (Estimate): December 11, 2013
• Last Update Submitted That Met QC Criteria: December 10, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: lipids; proteins; membrane; lipid raft
• Additional Relevant MeSH Terms: Wounds and Injuries
• Other Study ID Numbers: 31888-A; GM078054-01 (Other Identifier: National Institute of General Medical Sciences (NIGMS))