The reticuloendothelial system (RES) is important in defense against trauma, burn, sepsis and intravascular coagulation. Bioassayable and immunoreactive opsonic deficiency and RES phagocytic failure exists following major surgery, trauma and burn especially with sepsis. We will evaluate the importance of opsonic deficiency and RES failure in the etiology of organ failure following trauma. Our hypothesis is that posttrauma pulmonary insufficiency may be due to lung microembolization due to the coexistence of RES depression and increased blood-borne particulates. Plasma fibronectin (opsonin) deficiency may also exaggerate the increased lung vascular permeability with sepsis. Opsonic protein has been isolated and an immunoassay developed. It is identical to cold-insoluble globulin (CIg) or plasma fibronectin which has a high affinity for denatured collagen, fibrin and injured tissue. """"""""Plasma fibronectin"""""""" is antigenically related to the adhesive glycoprotein called """"""""cell surface fibronectin"""""""" which may be important to cell-cell contact and endothelial cell adherence. Plasma cryoprecipitate which is rich in opsonic protein (CIg) can reverse opsonic deficiency in septic injured patients and may improve cardiopulmonary function. We will perform animal and patient studies which may lead to a new therapy for septic injured patients. We will investigate: 1) the influence of surgery, trauma and burn on RES defense against sepsis and intravascular coagulation; 2) the mechanism mediating opsonic depletion after trauma and sepsis as well as its restoration; 3) the influence of opsonic therapy on lung localization of blood-borne particulates as well as survival to post-operative and post-trauma sepsis; 4) the influence of opsonic deficiency as well as replacement therapy on lung vascular permeability during sepsis and/or intravascular coagulation; 5) the influence of cryoprecipitate therapy on pulmonary function in septic trauma patients. Immunoreactive opsonic fibronectin may have value as a non-invasive index of RES function and reversal of opsonic deficiency may have therapeutic value in septic burn and trauma patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM021447-11
Application #
3270499
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1977-12-01
Project End
1986-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
11
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Albany Medical College
Department
Type
Schools of Medicine
DUNS #
City
Albany
State
NY
Country
United States
Zip Code
12208
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