Proteomics Reveals
a Role for Attachment in Monocyte
Differentiation into Efficient Proinflammatory Macrophages
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Abstract
Monocytes
are blood-borne cells of the innate immune system. They
can be differentiated and activated into proinflammatory macrophages
that might be employed in tumor immune therapy. Monocyte exposure
to lipopolysaccharide (LPS) is a standard method to induce a proinflammatory
macrophage state, with the resultant population comprising both adherent
and nonadherent cells. In the current study, we aimed to identify
the differences in proteomes of these monocyte subpopulations, which
addresses a more general question about the role of attachment in
monocyte differentiation. Label-free proteomics of a model of human
monocytes (THP-1 cell line) revealed that the cells remaining in suspension
upon LPS treatment were activated by cytokines and primed for rapid
responsiveness to pathogens. In terms of proteome change, the adhesion
process was orthogonal to activation. Adherent cells exhibited signs
of differentiation and enhanced innate immune responsivity, being
closer to macrophages. These findings indicate that adherent, LPS-treated
cells would be more appropriate for use in tumor therapeutic applications