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Sponsored by: |
National Institute of Allergy and Infectious Diseases (NIAID) |
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Information provided by: | National Institutes of Health Clinical Center (CC) |
ClinicalTrials.gov Identifier: | NCT00339287 |
Human phagocytic cells such as polymorphonuclear leukocytes (PMNs) are readily mobilized to sites of infection and ingest microorganisms by a process known as phagocytosis. The combined effects of reactive oxygen species (ROS) and proteolytic peptides and enzymes released into forming bacterial phagosomes kill most ingested bacteria. However, many human bacterial pathogens have devised means to subvert normal phagocyte responses and the innate immune response and cause severe disease.
The overall objective of this study is to elucidate specific features of pathogen-phagocyte interactions that underlie evasion of the innate immune response or contribute to the pathophysiology of disease or inflammatory disorders. Therefore, specific projects will:
The studies will be performed using multiple techniques including state-of-the-art equipment for genomics and proteomics strategies to identify target bacterial genes/proteins of interest or those up-regulated in phagocytes. Phagocyte-pathogen interactions will be examined using fluorescence-based real-time assays and video microscopy, confocal and electron microscopy in combination with enzymatic assays for ROS production, routine biochemistry, immunology and cell biology.
Implementing these studies will require isolation of phagocytic leukocytes from venous blood of healthy human volunteers. The study population will be all-inclusive except in certain instances where individuals possess genetic defects that impair phagocyte function (e.g., myeloperoxidase-deficiency) or have altered phagocyte function due to outside influences such as recent bacterial or viral infection.
The proposed studies will likely provide new information pertinent to understanding host cell-pathogen interactions and the pathophysiology of inflammatory conditions.
Condition |
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Macrophages Bacteria |
Study Type: | Observational |
Official Title: | Molecular Basis of Human Phagocyte Interactions With Bacterial Pathogens |
Estimated Enrollment: | 120 |
Study Start Date: | February 2001 |
Human phagocytic cells such as polymorphonuclear leukocytes (PMNs) are readily mobilized to sites of infection and ingest microorganisms by a process known as phagocytosis. The combined effects of reactive oxygen species (ROS) and proteolytic peptides and enzymes released into forming bacterial phagosomes kill most ingested bacteria. However, many human bacterial pathogens have devised means to subvert normal phagocyte responses and cause severe diseases in humans.
The overall objective of this study is to elucidate specific features of pathogen-phagocyte interactions that underlie evasion of the innate immune response or contribute to the pathophysiology of disease or inflammatory disorders. Therefore, projects will address 3 specific aims:
The studies will be performed using multiple techniques including state-of-the-art equipment for genomics and proteomics strategies to identify target bacterial genes/proteins of interest or those up-regulated in phagocytes. Phagocyte-pathogen interactions will be examined using fluorescence-based real-time assays and video microscopy, confocal and electron microscopy in combination with enzymatic assays for ROS production, routine biochemistry, immunology and cell biology.
Implementing these studies will require isolation of phagocytic leukocytes from venous blood of healthy human volunteers. The study population will be all-inclusive except in certain instances where individuals possess genetic defects that impair phagocyte function (e.g., myeloperoxidase-deficiency) or have altered phagocyte function due to outside influences such as recent bacterial or viral infection.
The proposed studies will likely provide new information pertinent to understanding host cell-pathogen interactions and the pathophysiology of inflammatory conditions.
Ages Eligible for Study: | 21 Years to 65 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Volunteers will be selected from a healthy adult population, 21-65 years of age, with no known medical problems and will generally be NIH employees working at Rocky Mountain Laboratories (RML) or within the community of Hamilton, MT.
No race or gender is excluded from the donor pool and reflects the diversity of the community and that of the employees at RML.
The specific criteria for eligibility are as follows:
Contact: Frank R. DeLeo, Ph.D. | (406) 363-9448 | fdeleo@niaid.nih.gov |
United States, Montana | |
NIAID, Rocky Mountain Laboratories | Recruiting |
Hamilton, Montana, United States, 59840 | |
Sub-Investigator: Ted Hackstadt, Ph.D. | |
Sub-Investigator: Jean Celli, Ph.D. |
Study ID Numbers: | 999901055, 01-I-N055 |
Study First Received: | June 19, 2006 |
Last Updated: | November 22, 2008 |
ClinicalTrials.gov Identifier: | NCT00339287 |
Health Authority: | United States: Federal Government |
Inflammation Innate Immunity Macrophages Neutrophils Pathogenesis |
Inflammation |