TY - JOUR
T1 - Dynamic macrophage "probing" is required for the efficient capture of phagocytic targets
AU - Flannagan, Ronald S.
AU - Harrison, Rene E.
AU - Yip, Christopher M.
AU - Jaqaman, Khuloud
AU - Grinstein, Sergio
PY - 2010/12/13
Y1 - 2010/12/13
N2 - Binding of ligands by immunoreceptors is thought to be a passive, stochastic process. Contrary to this notion, we found that binding of IgG-opsonized particles by Fcγ receptors was inhibited in macrophages, dendritic and microglial cells by agents that interfere with actin assembly or disassembly. Changes in the lateral mobility of the receptors - assessed by single-particle tracking - or in the microelasticity of the membrane - determined by atomic-force microscopy - could not account for the effects of actin disruption on particle binding. Instead, we found that the macrophages contact their targets by actively extending actin-rich structures. Formation of these protrusions is driven by Rac and requires phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. Capture of C3bi-opsonized as well as unopsonized targets by macrophages was also dependent on actin. Thus, phagocytes continuously probe their environment for foreign particles in a manner akin to the constitutive sampling of the fluid milieu by dendritic cells. Active probing by phagocytes is most important when confronted by scarcely opsonized and/or highly mobile targets.
AB - Binding of ligands by immunoreceptors is thought to be a passive, stochastic process. Contrary to this notion, we found that binding of IgG-opsonized particles by Fcγ receptors was inhibited in macrophages, dendritic and microglial cells by agents that interfere with actin assembly or disassembly. Changes in the lateral mobility of the receptors - assessed by single-particle tracking - or in the microelasticity of the membrane - determined by atomic-force microscopy - could not account for the effects of actin disruption on particle binding. Instead, we found that the macrophages contact their targets by actively extending actin-rich structures. Formation of these protrusions is driven by Rac and requires phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. Capture of C3bi-opsonized as well as unopsonized targets by macrophages was also dependent on actin. Thus, phagocytes continuously probe their environment for foreign particles in a manner akin to the constitutive sampling of the fluid milieu by dendritic cells. Active probing by phagocytes is most important when confronted by scarcely opsonized and/or highly mobile targets.
UR - http://www.scopus.com/inward/record.url?scp=78650162456&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650162456&partnerID=8YFLogxK
U2 - 10.1083/jcb.201007056
DO - 10.1083/jcb.201007056
M3 - Article
C2 - 21135140
AN - SCOPUS:78650162456
SN - 0021-9525
VL - 191
SP - 1205
EP - 1218
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 6
ER -