The leukocyte complement (C) system consists of eight types of membrane C receptors, various C components synthesized by leukocytes, and plasma C components that interact with leukocytes. The objective of this project is to characterize the function of the leukocyte C system.
The specific aims are as follows: (1) examine the in vitro immune response of lymphocytes and determine if the leukocyte C system has a role in recognition of alternative pathway (AP) activators through either factor B cleavage of membrane C5 or the binding of factor H (H) to membrane H receptors (H-R), characterize the suppression of lymphocyte activation by CR?2? (C3d-receptor) ligands and determine if this represents a mechanism for discrimination of nonactivators of the AP; (2) examine the role of the leukocyte C system in the tumoricidal activity of macrophages and natural killer cells; (3) determine whether serum- or effector cell-derived C3 is deposited onto AP-activating tumor cells and whether this represents an important mechanism for effector cell binding to tumor cells by way of C receptors; (4) examine the role of the leukocyte C system in the neutrophil respiratory burst response to zymosan and bacteria; and (5) determine whether either iC3b or specific carbohydrates contained in the microorganism cell walls trigger a respiratory burst and release of lysosomal enzymes through recognition by C receptor type three (CR?3?). (CS)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA025613-08
Application #
3166944
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1978-09-30
Project End
1987-11-30
Budget Start
1986-04-01
Budget End
1987-11-30
Support Year
8
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Myones, B L; Dalzell, J G; Hogg, N et al. (1988) Neutrophil and monocyte cell surface p150,95 has iC3b-receptor (CR4) activity resembling CR3. J Clin Invest 82:640-51
Myones, B L; Ross, G D (1987) Identification of a spontaneously shed fragment of B cell complement receptor type two (CR2) containing the C3d-binding site. Complement 4:87-98
Cain, J A; Newman, S L; Ross, G D (1987) Role of complement receptor type three and serum opsonins in the neutrophil response to yeast. Complement 4:75-86
Ross, G D; Cain, J A; Myones, B L et al. (1987) Specificity of membrane complement receptor type three (CR3) for beta-glucans. Complement 4:61-74
Ross, G D; Yount, W J; Walport, M J et al. (1985) Disease-associated loss of erythrocyte complement receptors (CR1, C3b receptors) in patients with systemic lupus erythematosus and other diseases involving autoantibodies and/or complement activation. J Immunol 135:2005-14
Ross, G D; Cain, J A; Lachmann, P J (1985) Membrane complement receptor type three (CR3) has lectin-like properties analogous to bovine conglutinin as functions as a receptor for zymosan and rabbit erythrocytes as well as a receptor for iC3b. J Immunol 134:3307-15
Ross, G D; Thompson, R A; Walport, M J et al. (1985) Characterization of patients with an increased susceptibility to bacterial infections and a genetic deficiency of leukocyte membrane complement receptor type 3 and the related membrane antigen LFA-1. Blood 66:882-90
Frade, R; Myones, B L; Barel, M et al. (1985) gp140, a C3b-binding membrane component of lymphocytes, is the B cell C3dg/C3d receptor (CR2) and is distinct from the neutrophil C3dg receptor (CR4). Eur J Immunol 15:1192-7