Kinetics of LFA-1 mediated adhesion of human neutrophils to ICAM-1--role of E-selectin signaling post-activation.
LFA-1 and Mac-1 are the two integrins involved in the arrest and firm adhesion of neutrophils. LFA-1 plays a role in the early stage of cell arrest while Mac-1 stabilizes firm adhesion. Here, we further elucidated the kinetics of LFA-1 activation and its role in mediating neutrophil adhesion to ICAM-1 in the presence of E-selectin interaction. We confirm that LFA-1 activation to high affinity is transient in nature, decaying back to low affinity within 1 min after chemotactic stimulation. However, we show for the first time that this downshift in LFA-1 affinity does not return back to the low affinity state when E-selectin interaction is present and active, but rather E-selectin signals an intermediate LFA-1 conformation through PI3-Kinase that maintains an intermediate level of neutrophil firm adhesion. We further show that this E-selectin signaling is capable of returning LFA-1 to the intermediate affinity conformation outside the 1-min window previously reported for LFA-1 functionality. While our work confirms a role for PI3-Kinase in neutrophil firm adhesion, we show that PI3-Kinase may not be important in the initial transition from rolling to firm arrest (i.e. LFA-1 shift from low to high affinity conformation occurring within seconds of chemotactic stimulation).
Eniola-Adefeso
Omolola
O
Department of Chemical Engineering, University of Michigan, 2300 Hayward Street, 3074 H. H. Dow Building, Ann Arbor, MI 48109-2136, USA. lolaa@umich.edu
Huang
Ryan B
RB
Smith
C Wayne
CW
D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D019040:E-Selectin / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007700:Kinetics; D007739:L Cells; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D018375:Neutrophil Activation; D009504:Neutrophils / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection
D018821:CD18 Antigens; D019040:E-Selectin; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1