Latency associated peptide has in vitro and in vivo immune effects independent of TGF-beta1.
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.
Ali
Naeem A
NA
Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America.
Gaughan
Alice A
AA
Orosz
Charles G
CG
Baran
Chris P
CP
McMaken
Sara
S
Wang
Yijie
Y
Eubank
Timothy D
TD
Hunter
Melissa
M
Lichtenberger
Frank J
FJ
Flavahan
Nicholas A
NA
Lawler
Jack
J
Marsh
Clay B
CB
D000818:Animals; D002465:Cell Movement; D002633:Chemotaxis; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D005260:Female; D007249:Inflammation; D016753:Interleukin-10 / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D053779:Latent TGF-beta Binding Proteins / Q000502:physiology*; D007962:Leukocytes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009000:Monocytes / Q000378:metabolism; D010455:Peptides / Q000737:chemistry*; D011509:Proteoglycans / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D004338:Drug Combinations; D007797:Laminin; D053779:Latent TGF-beta Binding Proteins; D010455:Peptides; D011509:Proteoglycans; D053773:Transforming Growth Factor beta1; C059485:matrigel; D016753:Interleukin-10; D003094:Collagen