Alloimmune Lung Injury Induced by Local Innate Immune Activation Through Inhaled Lipopolysaccharide

Garantziotis, Stavros; Palmer, Scott M.; Snyder, Laurie D.; Ganous, Tonya M.; Chen, Benny J.; Wang, Tie; Cook, Donald N.; Schwartz, David A.

doi:10.1097/01.tp.0000286040.85007.89

Cited by 43 publications

(40 citation statements)

References 25 publications

(30 reference statements)

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“…Tissue-limited TLR effects were also demonstrated in the lung in another murine bone marrow transplant model. Aerosolized administration of LPS resulted in lung GVHD lesions similar to lymphocytic bronchiolitis and obliterative bronchiolitis in a manner dependent on TLR4 expression by donor-derived hematopoietic cells (73). All three reports suggest a role of local inflammation for the recruitment of alloreactive cells to target tissues.…”

Section: Tlrs In the Effector Phase Of Allograft Rejectionmentioning

confidence: 99%

The Multiple Facets of Toll-Like Receptors in Transplantation Biology

et al. 2008

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Toll-like receptors (TLRs) belong to a family of pattern-recognition receptors for microbial products and endogenous molecules released by stressed cells. Experimental studies show that TLRs are involved in the process of acute allograft rejection and that their activation can prevent transplantation tolerance. Herein, we review the expression of TLRs and the impact of TLR signaling in different cell types in grafted organs including APCs, T and B lymphocytes, epithelial and endothelial cells. We then discuss the involvement of TLRs in the different phases of the rejection phenomenon and the impact of TLR-mediated events on regulatory circuits which dampen alloimmune responses.

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Section: Tlrs In the Effector Phase Of Allograft Rejectionmentioning

confidence: 99%

The Multiple Facets of Toll-Like Receptors in Transplantation Biology

et al. 2008

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“…This effect was dependent on TLR4 signaling, and treatment with a TLR4 antagonist could protect against lung injury after allogeneic HSCT. 48 The authors demonstrated that the absence of functional TLR4 in donor-derived hematopoietic cells abrogated the development of pulmonary damage, whereas the presence or absence of TLR4 on recipient structural lung tissue had no impact on lung injury after transplantation. Because the effects were a result of local activation of pulmonary innate immunity, as opposed to systemic innate immunity, the authors concluded that inhalation of LPS can promote the development of alloimmune lung injury after BMT independent from systemic GVHD.…”

mentioning

confidence: 99%

Graft-versus-host disease: regulation by microbe-associated molecules and innate immune receptors

Penack

Holler

Brink

2010

Blood

136

113

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Acute graft-versus-host disease (GVHD) remains the major obstacle to a more favorable therapeutic outcome of allogeneic hematopoietic stem cell transplantation (HSCT). GVHD is characterized by tissue damage in gut, liver, and skin, caused by donor T cells that are critical for antitumor and antimicrobial immunity after HSCT. One obstacle in combating GVHD used to be the lack of understanding the molecular mechanisms that are involved in the initiation phase of this syndrome. Recent research has demonstrated that interactions between microbial-associated molecules (pathogen-associated molecular patterns [PAMPs]) and innate immune receptors (pathogen recognition receptors [PRRs]), such as NOD-like receptors (NLRs) and Toll-like receptors (TLRs), control adaptive immune responses in inflammatory disorders. Polymorphisms of the genes encoding NOD2 and TLR4 are associated with a higher incidence of GVHD in HSC transplant recipients. Interestingly, NOD2 regulates GVHD through its inhibitory effect on antigen-presenting cell (APC) function. These insights identify important mechanisms regarding the induction of GVHD through the interplay of microbial molecules and innate immunity, thus opening a new area for future therapeutic approaches. This review covers current knowledge of the role of PAMPs and PRRs in the control of adaptive immune responses during inflammatory diseases, particularly GVHD.

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“…In previous studies, LPS was administered intravenously to imitate acute respiratory distress syndrome (ARDS) in different species, such as domestic pigs, rats, and sheep [35][36][37]. Intratracheal instillation was used in Guinea pigs, mice, and rats [38,39] . To our knowledge, there is only one study (Pompe et al) where LPS was administered intratracheally (through aerosol) in the pig [40].…”

Section: This Study Demonstrated That Lps Instillation Results In Lunmentioning

confidence: 99%