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Priming by chemokines restricts lateral mobility of the adhesion receptor LFA-1 and restores adhesion to ICAM-1 nano-aggregates on human mature dendritic cells.
- Source :
-
PloS one [PLoS One] 2014 Jun 19; Vol. 9 (6), pp. e99589. Date of Electronic Publication: 2014 Jun 19 (Print Publication: 2014). - Publication Year :
- 2014
-
Abstract
- LFA-1 is a leukocyte specific β2 integrin that plays a major role in regulating adhesion and migration of different immune cells. Recent data suggest that LFA-1 on mature dendritic cells (mDCs) may function as a chemokine-inducible anchor during homing of DCs through the afferent lymphatics into the lymph nodes, by transiently switching its molecular conformational state. However, the role of LFA-1 mobility in this process is not yet known, despite that the importance of lateral organization and dynamics for LFA-1-mediated adhesion regulation is broadly recognized. Using single particle tracking approaches we here show that LFA-1 exhibits higher mobility on resting mDCs compared to monocytes. Lymphoid chemokine CCL21 stimulation of the LFA-1 high affinity state on mDCs, led to a significant reduction of mobility and an increase on the fraction of stationary receptors, consistent with re-activation of the receptor. Addition of soluble monomeric ICAM-1 in the presence of CCL21 did not alter the diffusion profile of LFA-1 while soluble ICAM-1 nano-aggregates in the presence of CCL21 further reduced LFA-1 mobility and readily bound to the receptor. Overall, our results emphasize the importance of LFA-1 lateral mobility across the membrane on the regulation of integrin activation and its function as adhesion receptor. Importantly, our data show that chemokines alone are not sufficient to trigger the high affinity state of the integrin based on the strict definition that affinity refers to the adhesion capacity of a single receptor to its ligand in solution. Instead our data indicate that nanoclustering of the receptor, induced by multi-ligand binding, is required to maintain stable cell adhesion once LFA-1 high affinity state is transiently triggered by inside-out signals.
- Subjects :
- Chemokine CCL21 genetics
Chemokine CCL21 pharmacology
Dendritic Cells cytology
Dendritic Cells drug effects
Gene Expression Regulation
Humans
Intercellular Adhesion Molecule-1 genetics
Intercellular Adhesion Molecule-1 pharmacology
Ligands
Lymphocyte Function-Associated Antigen-1 genetics
Monocytes cytology
Monocytes drug effects
Primary Cell Culture
Protein Aggregates
Protein Binding
Protein Transport
Signal Transduction
Solubility
Chemokine CCL21 metabolism
Dendritic Cells metabolism
Intercellular Adhesion Molecule-1 metabolism
Lymphocyte Function-Associated Antigen-1 metabolism
Monocytes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24945611
- Full Text :
- https://doi.org/10.1371/journal.pone.0099589