Leukocytes express a large repertoire of adhesion molecules which play important roles in lymphocyte homing, in phagocytosis, and in the recruitment of leukocytes to sites of inflammation. Many of these cell- extracellular matrix and cell-cell adhesion molecules are members of the integrin family. Integrins are heterodimeric cell surface glycoproteins containing one alpha subunit and one beta subunit. Using the homology polymerase chain reaction method, we have identified a partial cDNA clone encoding a novel integrin alpha subunit, alpha-A, in lymphocytes. The proposed project aims to study the structure, expression, and function of alpha-A. First, the complete sequence of alpha-A will be determined by cDNA library screening. Second, Northern blot analysis will be used to quantitate alpha-A mRNA in T and B cells, in other leukocytes, and in non- leukocytes. The effects of T cell activation on alpha-A mRNA levels will also be examined. It has previously been shown that certain integrins are more highly expressed on lymphocytes found in certain organs, consistent with the hypothesis that these integrins are organ-specific homing receptors. In this proposal, in situ hybridization will be used to detect tissue-specific differences in lymphocyte alpha-A expression. Third, the alpha-A subunit protein will be identified using antisera raised against peptides modeled after the deduced alpha-A amino acid sequence. Beta subunits which associate with alpha-A will be identified in co- immunoprecipitation, immunodepletion, and Western blotting experiments. Finally, cell adhesion assays and affinity chromatography will be used to attempt to identify ligands of alpha-A-containing integrins. Potential ligands to be examined include a variety of extracellular matrix proteins and endothelial cell surface proteins. These studies are designed to be a first step toward the determination of the role of alpha-A-containing integrins in normal and pathological immune responses.

Project Start
Project End
Budget Start
Budget End
Support Year
17
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Briggs, F B S; Ramsay, P P; Madden, E et al. (2010) Supervised machine learning and logistic regression identifies novel epistatic risk factors with PTPN22 for rheumatoid arthritis. Genes Immun 11:199-208
Yazdany, Jinoos; Yelin, Edward (2010) Health-related quality of life and employment among persons with systemic lupus erythematosus. Rheum Dis Clin North Am 36:15-32, vii
Janssens, A Cecile J W; Steyerberg, Ewout W; Jiang, Yebin et al. (2006) Value of the HLA-DRB1 shared epitope for predicting radiographic damage in rheumatoid arthritis depends on the individual patient risk profile. J Rheumatol 33:2383-9
Katz, Patricia P (2006) Childbearing decisions and family size among women with rheumatoid arthritis. Arthritis Rheum 55:217-23
Yelin, Edward H; Trupin, Laura S; Katz, Patricia P (2005) Impact of managed care on the use of biologic agents for rheumatoid arthritis. Arthritis Rheum 53:423-30
Katz, Patricia P (2005) Use of self-management behaviors to cope with rheumatoid arthritis stressors. Arthritis Rheum 53:939-49
von Scheven, E; Elder, M E (2005) Association between beta2-glycoprotein I gene polymorphisms and pediatric SLE and antiphospholipid antibodies. Lupus 14:440-4
Yang, Nan; Li, Hongzhe; Criswell, Lindsey A et al. (2005) Examination of ancestry and ethnic affiliation using highly informative diallelic DNA markers: application to diverse and admixed populations and implications for clinical epidemiology and forensic medicine. Hum Genet 118:382-92
Seldin, Michael F; Morii, Takanobu; Collins-Schramm, Heather E et al. (2004) Putative ancestral origins of chromosomal segments in individual african americans: implications for admixture mapping. Genome Res 14:1076-84
Chang, Wenhan; Shoback, Dolores (2004) Extracellular Ca2+-sensing receptors--an overview. Cell Calcium 35:183-96

Showing the most recent 10 out of 111 publications