Latency associated peptide has in vitro and in vivo immune effects independent of TGF-β1

Abstract

Latency Associated Peptide (LAP) binds TGF-β1, forming a latent complex Currently, LAP is presumed to function only as a sequestering agent for active TGF-β1. Previous work show that LAP can induce epithelial cell migration, but effect on leukocyte have not been reported. Because of the multiplicity of immunologic processes in which TGF-β1 plays a role, we hypothesized that LAP could function independently to modulate immune response. In separate experiments we found that LAP promoted chemotaxis opf human monocytes and blocked inflammation in vivo in a murine model of the delayed-type hypersensitivity response (DTHR). These effects did not involve TGF-B1 activity. Further studies revealed that disruption of specific LAP thrombospondin-1 (TSP-1) interactions prevented LAP induced responses. The effect of LAP on DTH inhibition depended on IL-10. These data support a novel role for LAP in regulating monocyte trafficking and immune modulation. © 2008 Ali et al.