Cell adhesion: a partner for many
Cell adhesion is of vital importance for a number of cellular functions. Several molecular families of cell adhesion proteins are known, among which the most important are the integrins and their cellular and soluble ligands. Currently, 24 different integrins have been described. They are complex heterodimeric molecules and need activation to become adhesive. They are commonly grouped in subfamilies according to their {beta} chains.u?&w|], 百拇医药
Blood cells express at least members of the {beta} 1, {beta} 2, {beta} 3, and {beta} 7 integrin families, but none are found on mature red cells. The primary cellular ligands for the leukocyte-specific {beta} 2 integrins are the intercellular adhesion molecules (ICAM); 5 have been described. Platelets are known to adhere through the {alpha} IIb{beta} 3 integrin to fibrinogen. Among the ICAMs, ICAM-4 is unique due to its expression on erythroid cells. This molecule was originally described as a member of the LandsteinerWiener (LW) blood group of antigens, but subsequent cloning and adhesion assays showed that it is a member of the ICAM family of adhesion proteins.1 Its physiologic function has remained unknown, but it shows an interesting relationship to the Rh antigens.2 Thus, Rhnull cells lack the ICAM-4 molecule and they may be part of a large membrane protein complex. Whereas the other ICAMs specifically bind to {beta} 2 integrins, ICAM-4 has recently been found to interact with several types of integrins expressed on blood and endothelial cells.
In this issue, Mankelow and colleagues (page 1503) have used mutational analysis to map the binding site on ICAM-4 for {alpha} V integrins and visualized the binding site using a structural model based on the structure of ICAM-2. Interestingly, the binding site is located in the first immunoglobulin (Ig) domain adjacent to but partially separated from those previously described for {alpha} L{beta} 2 and {alpha} M{beta} 2. The binding site for {alpha} L{beta} 2 is also confined to the first Ig domain of ICAM-4, whereas the binding site for {alpha} M{beta} 2 also involves domain 2.3 A relatively large binding site also seems to be the case for ICAM-4 binding to the platelet integrin {alpha} IIb{beta} 3.4 The {alpha} 4{beta} 1 integrin is known to bind to leucine–aspartic acid–valine (LDV) sequences and the binding site on ICAM-4 is evidently different from those of the other integrins. Based on the mutational studies, Mankelow et al synthesized peptides that inhibited the ICAM-4/{alpha} V-integrin interaction. The active peptides are clearly different from those previously described to interfere with ICAM/{beta} 2, {alpha} 4{beta} 1,5 and {alpha} IIb{beta} 3 interactions. The findings that red cells may specifically bind through ICAM-4 to integrins expressed on all major types of blood and endothelial cells indicate that it may be possible to develop reagents specific for the different ICAM-4 (red cell)/integrin interactions. Because of the pivotal role of red cells in human physiology and disease such reagents would be of great value.
--- Carl G. Gahmberg!k, 百拇医药
University of Helsinki!k, 百拇医药
References!k, 百拇医药
Bailly P, Tontti E, Hermand P, et al. The red cell LW blood group protein is an intercellular adhesion molecule which binds to CD11/CD18 leukocyte integrins. Eur J Immunol. 1995;25: 3316-3320. [Medline] [Order article via Infotrieve]!k, 百拇医药
Gahmberg CG. Molecular characterization of the human red cell Rho(D) antigen. EMBO J. 1983;2: 223-227. [Medline] [Order article via Infotrieve]!k, 百拇医药
Hermand P, Huet M, Callebaut I, et al. Binding sites of leukocyte {beta} 2 integrins (LFA-1, Mac-1) on the human ICAM-4/LW blood group protein. J Biol Chem. 2000;275: 26002-26010. [Abstract/Free Full Text]!k, 百拇医药
Hermand P, Gane P, Huet M, et al. Red cell ICAM-4 is a novel ligand for platelet-activated {alpha} IIb{beta} 3 integrin. J Biol Chem. 2003;278: 4892-4898. [Abstract/Free Full Text]!k, 百拇医药
Spring FA, Parsons SF, Ortlepp S, et al. Intercellular adhesion molecule-4 binds {alpha} 4{beta} 1 and {alpha} v-family integrins through novel integrin-binding mechanisms. Blood. 2001;98: 458-466. [Abstract/Free Full Text]!k, 百拇医药
Related Articles in Blood Online :!k, 百拇医药
Identification of critical amino-acid residues on the erythroid intercellular adhesion molecule-4 (ICAM-4) mediating adhesion to {alpha} V integrins.!k, 百拇医药
Tosti J. Mankelow, Frances A. Spring, Stephen F. Parsons, R. Leo Brady, Narla Mohandas, Joel A. Chasis, and David J. Anstee Blood 2004 103: 1503-1508. [Abstract] [Full Text]
Blood cells express at least members of the {beta} 1, {beta} 2, {beta} 3, and {beta} 7 integrin families, but none are found on mature red cells. The primary cellular ligands for the leukocyte-specific {beta} 2 integrins are the intercellular adhesion molecules (ICAM); 5 have been described. Platelets are known to adhere through the {alpha} IIb{beta} 3 integrin to fibrinogen. Among the ICAMs, ICAM-4 is unique due to its expression on erythroid cells. This molecule was originally described as a member of the LandsteinerWiener (LW) blood group of antigens, but subsequent cloning and adhesion assays showed that it is a member of the ICAM family of adhesion proteins.1 Its physiologic function has remained unknown, but it shows an interesting relationship to the Rh antigens.2 Thus, Rhnull cells lack the ICAM-4 molecule and they may be part of a large membrane protein complex. Whereas the other ICAMs specifically bind to {beta} 2 integrins, ICAM-4 has recently been found to interact with several types of integrins expressed on blood and endothelial cells.
In this issue, Mankelow and colleagues (page 1503) have used mutational analysis to map the binding site on ICAM-4 for {alpha} V integrins and visualized the binding site using a structural model based on the structure of ICAM-2. Interestingly, the binding site is located in the first immunoglobulin (Ig) domain adjacent to but partially separated from those previously described for {alpha} L{beta} 2 and {alpha} M{beta} 2. The binding site for {alpha} L{beta} 2 is also confined to the first Ig domain of ICAM-4, whereas the binding site for {alpha} M{beta} 2 also involves domain 2.3 A relatively large binding site also seems to be the case for ICAM-4 binding to the platelet integrin {alpha} IIb{beta} 3.4 The {alpha} 4{beta} 1 integrin is known to bind to leucine–aspartic acid–valine (LDV) sequences and the binding site on ICAM-4 is evidently different from those of the other integrins. Based on the mutational studies, Mankelow et al synthesized peptides that inhibited the ICAM-4/{alpha} V-integrin interaction. The active peptides are clearly different from those previously described to interfere with ICAM/{beta} 2, {alpha} 4{beta} 1,5 and {alpha} IIb{beta} 3 interactions. The findings that red cells may specifically bind through ICAM-4 to integrins expressed on all major types of blood and endothelial cells indicate that it may be possible to develop reagents specific for the different ICAM-4 (red cell)/integrin interactions. Because of the pivotal role of red cells in human physiology and disease such reagents would be of great value.
--- Carl G. Gahmberg!k, 百拇医药
University of Helsinki!k, 百拇医药
References!k, 百拇医药
Bailly P, Tontti E, Hermand P, et al. The red cell LW blood group protein is an intercellular adhesion molecule which binds to CD11/CD18 leukocyte integrins. Eur J Immunol. 1995;25: 3316-3320. [Medline] [Order article via Infotrieve]!k, 百拇医药
Gahmberg CG. Molecular characterization of the human red cell Rho(D) antigen. EMBO J. 1983;2: 223-227. [Medline] [Order article via Infotrieve]!k, 百拇医药
Hermand P, Huet M, Callebaut I, et al. Binding sites of leukocyte {beta} 2 integrins (LFA-1, Mac-1) on the human ICAM-4/LW blood group protein. J Biol Chem. 2000;275: 26002-26010. [Abstract/Free Full Text]!k, 百拇医药
Hermand P, Gane P, Huet M, et al. Red cell ICAM-4 is a novel ligand for platelet-activated {alpha} IIb{beta} 3 integrin. J Biol Chem. 2003;278: 4892-4898. [Abstract/Free Full Text]!k, 百拇医药
Spring FA, Parsons SF, Ortlepp S, et al. Intercellular adhesion molecule-4 binds {alpha} 4{beta} 1 and {alpha} v-family integrins through novel integrin-binding mechanisms. Blood. 2001;98: 458-466. [Abstract/Free Full Text]!k, 百拇医药
Related Articles in Blood Online :!k, 百拇医药
Identification of critical amino-acid residues on the erythroid intercellular adhesion molecule-4 (ICAM-4) mediating adhesion to {alpha} V integrins.!k, 百拇医药
Tosti J. Mankelow, Frances A. Spring, Stephen F. Parsons, R. Leo Brady, Narla Mohandas, Joel A. Chasis, and David J. Anstee Blood 2004 103: 1503-1508. [Abstract] [Full Text]