Receptor utilization by phagocytic cells varies depending on the cell
type and the substrate involved. In macrophages, phagocytosis is
mediated by a variety of receptors including IgG-Fc, complement
receptors, CD36, and mannose receptors.
2 44 Recent
experiments have proposed a critical role for integrins in the
phagocytosis process in several different cell types.
8 20 Integrin receptors are transmembrane heterodimeric proteins whose
extracellular binding domains define substrate affinity and
specificity.
22 They play critical roles in attachment and
migration of cells, including RPE cells, through the ECM. The
preferential phagocytosis of fibronectin-coated beads in this study
suggested that RPE cells express integrins with a substrate affinity
for fibronectin.
23 45 This correlates well with attachment
studies that demonstrate that RPE cells have a clear substrate
preference for fibronectin.
36 Fibronectin is a
glycoprotein with at least two independent cell adhesive regions
with different receptor specificities. The cell adhesive region in the
central portion of fibronectin is made up of a RGD and a PHSRN sequence
that function in synergy, whereas the carboxyl-terminus contains LDV
and REDV sequences with additive effects.
46 Studies of
cultured human RPE cells have shown a wide spectrum of integrin
receptor expression, including β1, β2, β5, α1, α2, α3,α
4, α5, and α
M subunits.
22 23 In situ studies have recently shown the polarized expression ofα
vβ5 integrin on the apical surface of RPE cells and have proposed
a role for this integrin in retinal adhesion and ROS
phagocytosis.
8 9 23 Many integrins can bind fibronectin;
however, α5β1 is fibronectin- specific, is expressed on RPE cells,
and is the major fibronectin receptor on most cells.
22 23 α
5β1 interacts with the central cell adhesive region of fibronectin
and requires both RGD and synergy sites for maximal binding. The
antibody inhibition studies performed in the present study demonstrated
the clear preference for utilization of the α5β1 integrin for
fibronectin phagocytosis by RPE cells. The dose–response of anti-α5
antibody on fibronectin phagocytosis by RPE cells reveals that maximal
inhibition did not reach the level of nonspecific phagocytosis,
suggesting that there may be other less significant unknown receptors
involved in fibronectin phagocytosis by RPE cells. An interesting
difference between the phagocytosis of fibronectin by hematopoietic
cells and RPE cells is the involvement of the αvβ3 integrin. In
K562 cells transfected with αvβ3, antibodies against αvβ3
inhibit fibronectin phagocytosis by suppressing the phagocytic
competence of the α5β1 integrin.
20 This effect is not
present in fibronectin phagocytosis by RPE cells and may be related to
the low expression of αvβ3 in these cells.
9 23