Thrombospondin-1 triggers macrophage IL-10 production and promotes resolution of experimental lung injury

Y. Zhao; Z. Xiong; E. J. Lechner; P. A. Klenotic; B. J. Hamburg; M. Hulver; A. Khare; T. Oriss; N. Mangalmurti; Y. Chan; Y. Zhang; M. A. Ross; D. B. Stolz; M. R. Rosengart; J. Pilewski; P. Ray; A. Ray; R. L. Silverstein; J. S. Lee

doi:10.1038/mi.2013.63

Thrombospondin-1 triggers macrophage IL-10 production and promotes resolution of experimental lung injury

Y. Zhao, Z. Xiong, E. J. Lechner, P. A. Klenotic, B. J. Hamburg, M. Hulver, A. Khare, T. Oriss, N. Mangalmurti, Y. Chan, Y. Zhang, M. A. Ross, D. B. Stolz, M. R. Rosengart, J. Pilewski, P. Ray, A. Ray, R. L. Silverstein, J. S. Lee

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Abstract

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.

Original language	English
Pages (from-to)	440-448
Number of pages	9
Journal	Mucosal Immunology
Volume	7
Issue number	2
DOIs	https://doi.org/10.1038/mi.2013.63
State	Published - Mar 2014

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Zhao, Y., Xiong, Z., Lechner, E. J., Klenotic, P. A., Hamburg, B. J., Hulver, M., Khare, A., Oriss, T., Mangalmurti, N., Chan, Y., Zhang, Y., Ross, M. A., Stolz, D. B., Rosengart, M. R., Pilewski, J., Ray, P., Ray, A., Silverstein, R. L., & Lee, J. S. (2014). Thrombospondin-1 triggers macrophage IL-10 production and promotes resolution of experimental lung injury. Mucosal Immunology, 7(2), 440-448. https://doi.org/10.1038/mi.2013.63

@article{63ae157ebad4442dbfd720b340a34a31,

title = "Thrombospondin-1 triggers macrophage IL-10 production and promotes resolution of experimental lung injury",

abstract = "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 = "Y. Zhao and Z. Xiong and Lechner, {E. J.} and Klenotic, {P. A.} and Hamburg, {B. J.} and M. Hulver and A. Khare and T. Oriss and N. Mangalmurti and Y. Chan and Y. Zhang and Ross, {M. A.} and Stolz, {D. B.} and Rosengart, {M. R.} and J. Pilewski and P. Ray and A. Ray and Silverstein, {R. L.} and Lee, {J. S.}",

year = "2014",

month = mar,

doi = "10.1038/mi.2013.63",

language = "English",

volume = "7",

pages = "440--448",

journal = "Mucosal Immunology",

issn = "1933-0219",

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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, JS 2014, 'Thrombospondin-1 triggers macrophage IL-10 production and promotes resolution of experimental lung injury', Mucosal Immunology, vol. 7, no. 2, pp. 440-448. https://doi.org/10.1038/mi.2013.63

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T1 - Thrombospondin-1 triggers macrophage IL-10 production and promotes resolution of experimental lung injury

AU - Zhao, Y.

AU - Xiong, Z.

AU - Lechner, E. J.

AU - Klenotic, P. A.

AU - Hamburg, B. J.

AU - Hulver, M.

AU - Khare, A.

AU - Oriss, T.

AU - Mangalmurti, N.

AU - Chan, Y.

AU - Zhang, Y.

AU - Ross, M. A.

AU - Stolz, D. B.

AU - Rosengart, M. R.

AU - Pilewski, J.

AU - Ray, P.

AU - Ray, A.

AU - Silverstein, R. L.

AU - Lee, J. S.

PY - 2014/3

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N2 - 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.

AB - 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.

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DO - 10.1038/mi.2013.63

M3 - Article

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AN - SCOPUS:84895085298

SN - 1933-0219

VL - 7

SP - 440

EP - 448

JO - Mucosal Immunology

JF - Mucosal Immunology

IS - 2

ER -

Thrombospondin-1 triggers macrophage IL-10 production and promotes resolution of experimental lung injury

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