Latency associated peptide has in vitro and in vivo immune effects independent of TGF-beta1.

• Main Authors: Naeem A Ali, Alice A Gaughan, Charles G Orosz, Chris P Baran, Sara McMaken, Yijie Wang, Timothy D Eubank, Melissa Hunter, Frank J Lichtenberger, Nicholas A Flavahan, Jack Lawler, Clay B Marsh
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2008-04-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC2288562?pdf=render

Latency Associated Peptide (LAP) binds TGF-beta1, forming a latent complex. Currently, LAP is presumed to function only as a sequestering agent for active TGF-beta1. Previous work shows that LAP can induce epithelial cell migration, but effects on leukocytes have not been reported. Because of the multiplicity of immunologic processes in which TGF-beta1 plays a role, we hypothesized that LAP could function independently to modulate immune responses. In separate experiments we found that LAP promoted chemotaxis of human monocytes and blocked inflammation in vivo in a murine model of the delayed-type hypersensitivity response (DTHR). These effects did not involve TGF-beta1 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.