The interactions between plasma proteins of the complement and properdin systems and cells, especially formed elements of the blood, will be examined. In one line of experiments, cells will be used as targets in model systems to elucidate the mechanisms of interaction of the alternative pathway proteins. Erythrocytes coated with purified constituents of this pathway will be used to investigate further the function and mechanisms of the control proteins, C3b Inactivator and beta 1H globulin. The precise mode of interaction of these two proteins with the target substrate C3b will be determined. Erythrocytes coated with specific antibody immunoglobulins will be used to explore further the way in which IgG enhances the formation of the alternative pathway convertase, and the potential role of other immunoglobulin classes in alternative pathway activation will be studied. In the second line of experiments the biologic consequences of interaction between activated complement proteins and leukocytes will be examined. The recent finding that C3 receptors on mast cells enhance endocytosis by these cells will be extended, particularly in regard to the release of low molecular weight mediators. The capacity of lysosomal proteases from neutrophils to function in the degradation of C3b' will be extended, particularly in regard to the release of low molecular weight mediators. The capacity of lysosomal proteases from neutrophils to function in the degradation of C3b' will be studied and the fate of C3 bound to an immune complex and subsequently endocytosed by a neutrophil will be determined. Effects of the binding of activated complement components to receptors on monocytes will be sought.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI013049-10
Application #
3125360
Study Section
Experimental Immunology Study Section (EI)
Project Start
1976-05-01
Project End
1986-04-30
Budget Start
1985-05-01
Budget End
1986-04-30
Support Year
10
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Type
Schools of Medicine
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298
Whiteman, L Y; Purkall, D B; Ruddy, S (1995) Covalent linkage of C3 to properdin during complement activation. Eur J Immunol 25:1481-4
Whiteman, L Y; Purkall, D B; Ruddy, S (1991) Association of activated properdin with complexes of properdin with C3. J Immunol 147:1344-51
Gervasoni Jr, J E; Ruddy, S (1989) Binding of human C3a and the synthetic nonapeptide C3a (tyr-70-77) to rat peritoneal mast cells. Prog Clin Biol Res 297:221-31;discussion 231-2
Willis, H E; Browder, B; Feister, A J et al. (1988) Monoclonal antibody to human IgG Fc receptors. Cross-linking of receptors induces lysosomal enzyme release and superoxide generation by neutrophils. J Immunol 140:234-9
Feister, A J; Browder, B; Willis, H E et al. (1988) Pertussis toxin inhibits human neutrophil responses mediated by the 42-kilodalton IgG Fc receptor. J Immunol 141:228-33
Moxley, G; Ruddy, S (1987) Elevated plasma C3 anaphylatoxin levels in rheumatoid arthritis patients. Arthritis Rheum 30:1097-104
Gelfand, E W; Rao, C P; Minta, J O et al. (1987) Inherited deficiency of properdin and C2 in a patient with recurrent bacteremia. Am J Med 82:671-5
Eby, W M; Irby, W R; Irby, J H et al. (1987) Recurrent meningitis with familial C8 deficiency: case report. Va Med 114:91-4
Gervasoni Jr, J E; Conrad, D H; Hugli, T E et al. (1986) Degradation of human anaphylatoxin C3a by rat peritoneal mast cells: a role for the secretory granule enzyme chymase and heparin proteoglycan. J Immunol 136:285-92