PMID- 10438935
OWN - NLM
STAT- MEDLINE
DCOM- 19990909
LR  - 20171116
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 163
IP  - 4
DP  - 1999 Aug 15
TI  - The leukocyte integrin alpha D beta 2 binds VCAM-1: evidence for a binding
      interface between I domain and VCAM-1.
PG  - 1984-90
AB  - The trafficking of leukocytes through tissues is supported by an interaction
      between the beta 2 (CD18) integrins CD11a/CD18 (LFA-1) and CD11b/CD18 (Mac-1) and
      their ligand ICAM-1. The most recently identified and fourth member of the beta 2
      integrins, alpha D beta 2, selectively binds ICAM-3 and does not appear to bind
      ICAM-1. We have reported recently that alpha D beta 2 can support eosinophil
      adhesion to VCAM-1. Here we demonstrate that expression of alpha D beta 2 in a
      lymphoid cell that does not express alpha 4 integrins confers efficient binding
      to VCAM-1. In addition, a soluble form of alpha D beta 2 binds VCAM-1 with
      greater efficiency relative to ICAM-3. The I domain of alpha D contains a binding
      site for VCAM-1 since recombinant alpha D I domain binds specifically to VCAM-1. 
      In addition, alpha D mAb that block cellular binding to VCAM-1 bind the alpha D I
      domain. Using VCAM-1 mutants we have determined that the binding site on VCAM-1
      for alpha D beta 2 overlaps with that of alpha 4++ integrins. Substitution of
      VCAM-1 aspartate at position 40, D40, within the conserved integrin binding site,
      diminishes binding to alpha D beta 2 and abrogates binding to the alpha D I
      domain. The corresponding integrin binding site residue in ICAM-3 is also
      essential to alpha D beta 2 binding. Finally, we demonstrate that alpha D beta 2 
      can support lymphoid cell adhesion to VCAM-1 under flow conditions at levels
      equivalent to those mediated by alpha 4 beta 1. These results indicate that
      VCAM-1 can bind to an I domain and that the binding of alpha D beta 2 to VCAM-1
      may contribute to the trafficking of a subpopulation of leukocytes that express
      alpha D beta 2.
FAU - Van der Vieren, M
AU  - Van der Vieren M
AD  - ICOS Corp., Bothell, WA 98021, USA.
FAU - Crowe, D T
AU  - Crowe DT
FAU - Hoekstra, D
AU  - Hoekstra D
FAU - Vazeux, R
AU  - Vazeux R
FAU - Hoffman, P A
AU  - Hoffman PA
FAU - Grayson, M H
AU  - Grayson MH
FAU - Bochner, B S
AU  - Bochner BS
FAU - Gallatin, W M
AU  - Gallatin WM
FAU - Staunton, D E
AU  - Staunton DE
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antibodies, Blocking)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD)
RN  - 0 (CD11 Antigens)
RN  - 0 (ITGAD protein, human)
RN  - 0 (Integrin alpha Chains)
RN  - 0 (Integrins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Cytoadhesin)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 143198-26-9 (Integrin alpha4)
SB  - AIM
SB  - IM
MH  - Animals
MH  - Antibodies, Blocking/metabolism
MH  - Antibodies, Monoclonal/metabolism
MH  - Antigens, CD/genetics/metabolism
MH  - Binding Sites/genetics/immunology
MH  - Binding Sites, Antibody
MH  - CD11 Antigens
MH  - Cell Adhesion/immunology
MH  - Cell Movement/immunology
MH  - Humans
MH  - Integrin alpha Chains
MH  - Integrin alpha4
MH  - Integrins/biosynthesis/genetics/immunology/*metabolism
MH  - Jurkat Cells
MH  - Leukocytes/immunology/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Peptide Fragments/chemistry/genetics/*metabolism
MH  - Protein Binding/genetics/immunology
MH  - *Receptors, Cytoadhesin
MH  - Recombinant Proteins/metabolism
MH  - Rheology
MH  - Vascular Cell Adhesion Molecule-1/*metabolism
EDAT- 1999/08/10 00:00
MHDA- 1999/08/10 00:01
CRDT- 1999/08/10 00:00
PHST- 1999/08/10 00:00 [pubmed]
PHST- 1999/08/10 00:01 [medline]
PHST- 1999/08/10 00:00 [entrez]
AID - ji_v163n4p1984 [pii]
PST - ppublish
SO  - J Immunol. 1999 Aug 15;163(4):1984-90.