Characterization of four CD18 mutants in leucocyte adhesion deficient (LAD) patients with differential capacities to support expression and function of the CD11/CD18 integrins LFA-1, Mac-1 and p150,95
Shaw, J.M., Al-Shamkhani, A., Boxer, L.A., Buckley, C.D., Dodds, A.W., Klein, N., Nolan, S.M., Roberts, I., Roos, D., Scarth, S.L., Simmons, D.L., Tan, S.M. and Law, S.K.A. (2001) Characterization of four CD18 mutants in leucocyte adhesion deficient (LAD) patients with differential capacities to support expression and function of the CD11/CD18 integrins LFA-1, Mac-1 and p150,95. Clinical and Experimental Immunology, 126, (2), 311-318. (doi:10.1046/j.1365-2249.2001.01661.x).
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Description/Abstract
Leucocyte adhesion deficiency (LAD) is a hereditary disorder caused by mutations in the CD18 (β2 integrin) gene. Four missense mutations have been identified in three patients. CD18(A270V) supports, at a diminished level, CD11b/CD18 (Mac-1, αMβ2 integrin) and CD11c/CD18 (p150,95, αXβ2 integrin) expression and function but not CD11a/CD18 (LFA-1, αLβ2 integrin) expression. Conversely, CD18(A341P) supports a limited level of expression and function of CD11a/CD18, but not of the other two CD11/CD18 antigens. CD18(C590R) and CD18(R593C) show a decreasing capacity to associate with the CD11a, CD11c and CD11b subunits. Transfectants expressing the CD11a/CD18 with the C590R and R593C mutations are more adhesive than transfectants expressing wild-type LFA-1, and express the reporter epitope of the monoclonal antibody 24 constitutively. Thus, the four mutations affect CD18 differently in its capacities to support CD11/CD18 expression and adhesion. These results not only provide a biochemical account for the clinical diversity of patients with leucocyte adhesion deficiency, but also offer novel insights into the structural basis of interaction between the α and β subunits, which is an integral component in our understanding of integrin-mediated adhesion and its regulation.
| Item Type: | Article |
|---|---|
| Related URLs: | |
| Subjects: | R Medicine > R Medicine (General) Q Science > QH Natural history > QH426 Genetics |
| Divisions: | University Structure - Pre August 2011 > School of Medicine > Cancer Sciences |
| Item ID: | 26603 |
| Date Deposited: | 20 Apr 2006 |
| Last Modified: | 01 Jun 2011 08:51 |
| Contributors: | Shaw, J.M. (Author) Al-Shamkhani, A. (Author) Boxer, L.A. (Author) Buckley, C.D. (Author) Dodds, A.W. (Author) Klein, N. (Author) Nolan, S.M. (Author) Roberts, I. (Author) Roos, D. (Author) Scarth, S.L. (Author) Simmons, D.L. (Author) Tan, S.M. (Author) Law, S.K.A. (Author) |
| Date: | 2001 |
| Status: | Published |
| Contact Email Address: | alaw@molbiol.ox.ac.uk |
| URI: | http://eprints.soton.ac.uk/id/eprint/26603 |
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