Signal regulatory protein-? (SIRP-?) is a membrane
glycoprotein with regulatory properties from signal regulatory protein family
expressed mainly in myeloid cells, stem cells and neurons. It has been shown
that SIRP-? acts as an inhibitory receptor and interacts with a very common trans
membrane protein called CD47, which is also known as the “don´t eat
me” signal within most mammalian immune systems. This interaction can
negatively affect effector function of immune cells such as those in host cell
phagocytosis. SIRP-? diffuses across the macrophage membrane and accumulates at
synapses that attribute to phagocytosis in order to bind CD47, thusly
inhibiting the process of phagocytosis by the macrophage 1. The
binding of CD47 is known to be the “self” signal that prevents macrophages from
attacking healthy self-cells. The majority of this mechanism has been studied
through the regulation of CD47 and how it contributes to this signal of “self”
within an immune response.
The CD47-SIRP? interaction was
first explained by Oldenborg et al. 2, who demonstrated
erythrophagocytosis in the spleen and that the lack of tyrosine phosphorylation
in SIRP-? was associated with greater uptake of macrophages. It was later shown
that the extracellular domain of SIRP-? binds to CD47 and thusly transmits
itself throughout the cytoplasmic region of the target cell. In line with the
role of the CD47-SIRP? interaction in inhibiting phagocytosis by macrophages,
studies also showed that tumor cells are also culpable of overexpressing CD47
as a way to prevent the body’s immune response to destroying them 3.
Although these studies are very
elucidating, there has yet to be an experiment that characterizes macrophage
behavior without SIRP-? present. In order to best understand the CD47-SIRP?
mechanism an experiment proposed here builds off a previous study of CD47
inhibition within an inflammatory response 4. Characterization of
macrophage behavior under a SIRP-? missing condition will elucidate how to
better control macrophage behavior in disease therapies. In this study we
explore how macrophage behavior changes in response to the removal of the SIRP-?
receptor in THP-1 cells.