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 Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI027771-12
Application #
3142003
Study Section
Experimental Immunology Study Section (EI)
Project Start
1988-08-01
Project End
1993-07-31
Budget Start
1991-08-01
Budget End
1993-07-31
Support Year
12
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Louisville
Department
Type
Schools of Medicine
DUNS #
City
Louisville
State
KY
Country
United States
Zip Code
40292
Yan, J; Vetvicka, V; Xia, Y et al. (2000) Critical role of Kupffer cell CR3 (CD11b/CD18) in the clearance of IgM-opsonized erythrocytes or soluble beta-glucan. Immunopharmacology 46:39-54
Vyytvicka, V; Hanikyrova, M; Vyytvickova, J et al. (1999) Regulation of CR3 (CD11b/CD18)-dependent natural killer (NK) cell cytotoxicity by tumour target cell MHC class I molecules. Clin Exp Immunol 115:229-35
Yan, J; Vetvicka, V; Xia, Y et al. (1999) Beta-glucan, a ""specific"" biologic response modifier that uses antibodies to target tumors for cytotoxic recognition by leukocyte complement receptor type 3 (CD11b/CD18). J Immunol 163:3045-52
Xia, Y; Vetvicka, V; Yan, J et al. (1999) The beta-glucan-binding lectin site of mouse CR3 (CD11b/CD18) and its function in generating a primed state of the receptor that mediates cytotoxic activation in response to iC3b-opsonized target cells. J Immunol 162:2281-90
Xia, Y; Ross, G D (1999) Generation of recombinant fragments of CD11b expressing the functional beta-glucan-binding lectin site of CR3 (CD11b/CD18). J Immunol 162:7285-93
Reddy, R K; Xia, Y; Hanikyrova, M et al. (1998) A mixed population of immature and mature leucocytes in umbilical cord blood results in a reduced expression and function of CR3 (CD11b/CD18). Clin Exp Immunol 114:462-7
Vetvicka, V; Thornton, B P; Wieman, T J et al. (1997) Targeting of natural killer cells to mammary carcinoma via naturally occurring tumor cell-bound iC3b and beta-glucan-primed CR3 (CD11b/CD18). J Immunol 159:599-605
Thornton, B P; Vyytvicka, V; Pitman, M et al. (1996) Analysis of the sugar specificity and molecular location of the beta-glucan-binding lectin site of complement receptor type 3 (CD11b/CD18). J Immunol 156:1235-46
Pryzwansky, K B (1994) High voltage immunoelectron microscopy of complement receptor type 3-mediated capping and internalization of group A streptococcal cell walls by human neutrophils. Microsc Res Tech 28:263-76
Vyytvicka, V; Vyyktvickova, J; Fusek, M (1994) Effect of human procathepsin D on proliferation of human cell lines. Cancer Lett 79:131-5

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