| Literature References | 1. GAHMBERG, C,G., TOLVANEN, M. AND KOTOVUORI, P.
Leukocyte adhesion. Structure and function of human leukocyte
beta2-integrins and their cellular ligands.
EUR.J.BIOCHEMISTRY 245 215-232 (1997).
2. LEE, Y. W., KUHN, H., HENNIG, B., NEISH, A.S. AND TOBOREK, M.
IL-4 induced oxidative stress upregulates VCAM-1 gene expression in human
endothelial cells.
J.MOL.CELL.CARDIO. 33 83-94 (2001).
3. STANLEY, P., MCDOWALL, A. BATES, P.A., BRASHAW, J. AND HOGG, N.
The second domain of intercellular adhesion molecule-1 (ICAM-1) maintains
the structural integrity of the leukocyte function-associated antigen-1
BIOCHEM.J. 351 79-86 (2000).
4. BELLA, J., KOLATKAR, P.R., MARLOR, C.W., GREVE, J.M. AND ROSSMANN, M.G.
The structure of the two amino-terminal domains of human ICAM-1 suggests
how it functions as a rhinovirus receptor and as an LFA-1 integrin ligand.
PROC.NATL.ACAD.SCI.U.S.A. 95 4140-4145(1998).
5. KOTOVUORI, A., PESSA-MORIKAWA, T., KOTOVUORI, P., NORTAMO, P. AND
GAHMBERG, C.G.
ICAM-2 and a peptide from its binding domain are efficient activators
of leukocyte adhesion and integrin affinity.
PROC.NATL.ACAD.SCI.U.S.A. 96 3017-3022 (1999).
6. NEELAMEGHAM, S., TAYLOR, A.D., SHANKARAN, H., SMITH, W.C. AND SIMON, S.I.
Shear and time-depeneant changes in Mac-1, LFA, and ICAM-3 binding
regulate neutrophil homotypic adhesion.
J.IMMUNOL. 164 3798-3805 (2000).
7. HERMAND, P., HUET, M., CALLEBAUT, I., GANE, P., IHANUS, E.,
GAHMBERG, C.G., CARTRON, J.P. AND BAILLY, P.
Binding sites of leukocyte beta 2-integrins (LFA-1, MAC-1) on the human
ICAM-4/LW blood group protein.
J.BIOL.CHEM. 275 26002-26010 (2000).
8. TIAN, L., KILGANNON, P., YOSHIHARA, Y., MORI, K., GALLATIN, W.M.,
CARPEN, O. AND GAHMBERG, C.G.
Binding of T lymphocytes to hippocampal neurons through ICAM-5
integrin CD11a/CD18.
EUR.J.IMMUNOL. 30 810-818 (2000).
|
| Documentation | Intercellular adhesion molecules (ICAMs) are part of the immunoglobulin
superfamily. They are important in inflammation, immune responses and in
intracellular signalling events [1].
The ICAM family consists of five members, designated ICAM-1 to ICAM-5. They
are known to bind to leucocyte integrins CD11/CD18 during inflammation and
in immune responses. In addition, ICAMs may exist in soluble forms in human
plasma, due to activation and proteolysis mechanisms at cell surfaces [1].
ICAM-1 (CD54) contains five Ig-like domains. It is expressed on leucocytes,
endothelial and epithelial cells, and is upregulated in response to
bacterial invasion. The protein is a receptor for CD11a,b/CD18 (also termed
leukocyte-function associated (LFA) anitgen), fibrinogen, human rhinoviruses
and plasmodium falciparum-infected erythrocytes. ICAM-1binding sites for
CD11a/CD18 and its other binding partners are located in the first domain
and are overlapping. ICAM-1 domain 2 seems to play an important role in
maintaining the conformation of domain 1 and particularly the structural
integrity of the LFA-1 ligand-binding site [3].
The 3-dimensional atomic structure of the tandem N-terminal Ig-like domains
(D1 and D2) of ICAM-1 has been determined to 2.2A resolution and fitted into
a cryoelectron microscopy reconstruction of a rhinovirus-ICAM-1 complex [4].
Extensive charge interactions between ICAM-1 and human rhinoviruses are
largely conserved in major and minor receptor groups of rhinoviruses [4].
The interaction of ICAMs with LFA-1 is mediated by a divalent cation bound
to the insertion (I)-domain on the alpha chain of LFA-1 and the carboxyl
group of a conserved glutamic acid residue on ICAMs [4].
ICAM-2 (CD102) has two Ig-like domains. It is expressed on endothelial
cells, leucocytes and platelets, and binds to CD11a,b/CD18. The protein is
refractory to proinflammatory cytokines, and plays an important role in the
adhesion of leucocytes to the uninduced endothelium [5].
ICAM-3 (CD50) contains five Ig-like domains and binds to leucocyte integrins
CD11a,d/CD18. The protein plays an important role in the immune response and
perhaps in signal transduction [6].
ICAM-4 (LW blood group Ag) is red blood cell (RBC) specific and binds to
CD11a,b/CD18. It is associated with the RBC Rh antigens and could be
important in retaining immature red cells in the bone marrow, or in the
uptake of senescent cells into the spleen [7].
ICAM-5 (telencephalin) has nine Ig-like domains and is confined to the
telencephalon of the brain. The role of this CD11a/CD18 binding molecule
is not yet known [8].
ICAM is a 3-element fingerprint that provides a signature for the ICAM
family of adhesion molecules. The fingerprint was derived from an initial
alignment of 6 sequences: the motifs were drawn from conserved regions
towards the N-terminal portion of the alignment - motif 1 lies within the
N-terminal region of domain 2; and motifs 2 and 3 lie in the N-terminal
region of the extracellular domain. Two iterations on SPTR39_14f were
required to reach convergence, at which point a true set comprising 14
sequences was identified. A single partial match was also found, Q9Z133, a
testicular cell adhesion molecule 1 (TCAM1) from Rattus norvegicus that
matches motifs 2 and 3.
|