Thrombospondin-1 triggers macrophage IL-10 production and promotes resolution of experimental lung injury. Mucosal Immunol 2014 Mar;7(2):440-8
Date
09/21/2013Pubmed ID
24045574Pubmed Central ID
PMC3945733DOI
10.1038/mi.2013.63Scopus ID
2-s2.0-84895085298 (requires institutional sign-in at Scopus site) 57 CitationsAbstract
Mononuclear phagocyte recognition of apoptotic cells triggering suppressive cytokine signaling is a key event in inflammation resolution from injury. Mice deficient in thrombospondin (TSP)-1 (thbs1⁻/⁻), an extracellular matrix glycoprotein that bridges cell-cell interactions, are prone to lipopolysaccharide-induced lung injury and show defective macrophage interleukin (IL)-10 production during the resolution phase of inflammation. Reconstitution of IL-10 rescues thbs1⁻/⁻ mice from persistent neutrophilic lung inflammation and injury and thbs1⁻/⁻ alveolar macrophages show defective IL-10 production following intratracheal instillation of apoptotic neutrophils despite intact efferocytosis. Following co-culture with apoptotic neutrophils, thbs1⁻/⁻ macrophages show a selective defect in IL-10 production, whereas prostaglandin E2 and transforming growth factor beta 1 responses remain intact. Full macrophage IL-10 responses require the engagement of TSP-1 structural repeat 2 domain and the macrophage scavenger receptor CD36 LIMP-II Emp sequence homology (CLESH) domain in vitro. Although TSP-1 is not essential for macrophage engulfment of apoptotic neutrophils in vivo, TSP-1 aids in the curtailment of inflammatory responses during the resolution phase of injury in the lungs by providing a means by which apoptotic cells are recognized and trigger optimal IL-10 production by macrophages.
Author List
Zhao Y, Xiong Z, Lechner EJ, Klenotic PA, Hamburg BJ, Hulver M, Khare A, Oriss T, Mangalmurti N, Chan Y, Zhang Y, Ross MA, Stolz DB, Rosengart MR, Pilewski J, Ray P, Ray A, Silverstein RL, Lee JSAuthor
Roy L. Silverstein MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
CD36 Antigens
Dinoprostone
Disease Models, Animal
Interleukin-10
Lipopolysaccharides
Lung Injury
Macrophages
Mice
Mice, Knockout
Neutrophils
Pneumonia
Protein Interaction Domains and Motifs
Signal Transduction
Thrombospondin 1
Transforming Growth Factor beta1