Lipoxin A<sub>4</sub> inhibits immune cell binding to salivary epithelium and vascular endothelium

Chinthamani, Sreedevi; Odusanwo, Olutayo; Mondal, Nandini; Nelson, James W.; Neelamegham, Sriram; Baker, Olga J.

doi:10.1152/ajpcell.00259.2011

Cited by 29 publications

(22 citation statements)

References 95 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HMVECs express both the BLT1 and the BLT2 receptors on their surface and increase ICAM-1 and release chemokines in response to proinflammatory stimuli resulting in PMN adhesion. 20,[24][25][26][27][28] Previous data demonstrated that leukotriene B4-mediated HMVEC activation occurred via the BLT2 receptor in congruence with the presented data, and the BLT2 receptor has been implicated in other pulmonary diseases and angiogenesis. 20,[29][30][31] Furthermore, the concentration of LPS employed as a positive control may also seem excessive; however, it is based on the human response to injected LPS in which concentrations of 10 ng/mL injected induced hypotensive shock and a concentration of 500 ng/mL induced both shock and signs of ALI and not just fevers and changes in cytokine profiles.…”

Section: Discussionsupporting

confidence: 88%

Supernatants and lipids from stored red blood cells activate pulmonary microvascular endothelium through the BLT2 receptor and protein kinase C activation

et al. 2017

View full text Add to dashboard Cite

Background Although transfusion is a life-saving intervention, it may be associated with significant morbidity in injured patients. We hypothesize that stored red blood cells induce pro-inflammatory activation of human pulmonary microvascular endothelium (HMVECs) resulting in neutrophil (PMN) adhesion and predisposition to acute lung injury (ALI). Methods Ten units of red blood cells (RBCs) were collected and 50% (by weight) were leukoreduced (LR-RBCs) and the remainder was unmodified and stored in additive solution-5 (AS-5). Another 10 units of RBCs were collected, leukoreduced, and stored in AS-3. HMVECs were incubated with [10–40%]FINAL of the supernatants day (D)1-D42 of storage, lipid extracts and purified lipids. Endothelial surface expression of ICAM-1, IL-8 release, and PMN adhesion to HMVECs were measured. HMVEC signaling via the BLT2 receptor was evaluated. Supernatants and lipids were also employed as the first event in a two-event model of ALI. Results The supernatants [10–40%]FINAL from D21 LR-RBCs and D42 RBCs and LR-RBCs and the lipids from D42 stored in AS-5 induced increased ICAM-1 surface expression on endothelium, IL-8 release, and PMN adhesion. In addition, the supernatants [20–40%]FINAL from D21 and D42 RBCs in AS-5 also increased endothelial surface expression of ICAM-1. D42 supernatants and lipids also caused co-precipitation of β-arrestin-1 with BLT2, PKCβI, and PKCδand served as the first event in a two-event rodent model of ALI. In conclusion, lipids that accumulate during RBC storage activate endothelium and predispose to ALI, which may explain some of the adverse events associated with the transfusion of critically injured patients.

show abstract

Section: Discussionsupporting

confidence: 88%

Supernatants and lipids from stored red blood cells activate pulmonary microvascular endothelium through the BLT2 receptor and protein kinase C activation

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Although FPR1 and FPR2 share 69% sequence identity, FPR2 displays low affinity binding to the prototyoic formyl peptide, N-formyl-Met-Leu-Phe (fMLF) and many potent formyl peptide agonists for FPR1 4 . However, FPR2 can recognize a wider array of ligands with different structures and functions, which include not only bacterially derived formyl peptides but also non-formyl peptides, lipid mediators such as lipoxin A4 (LXA4), small molecules and proteins 2,5,6 , making this receptor one of the most promiscuous GPCRs characterized to date. How FPR2 is able to recognize and bind these ligands and transduce both proinflammatory and anti-inflammatory signals remains a mystery.…”

mentioning

confidence: 99%

Structural basis of ligand binding modes at the human formyl peptide receptor 2

et al. 2020

View full text Add to dashboard Cite

The human formyl peptide receptor 2 (FPR2) plays a crucial role in host defense and inflammation, and has been considered as a drug target for chronic inflammatory diseases. A variety of peptides with different structures and origins have been characterized as FPR2 ligands. However, the ligand-binding modes of FPR2 remain elusive, thereby limiting the development of potential drugs. Here we report the crystal structure of FPR2 bound to the potent peptide agonist WKYMVm at 2.8 Å resolution. The structure adopts an active conformation and exhibits a deep ligand-binding pocket. Combined with mutagenesis, ligand binding and signaling studies, key interactions between the agonist and FPR2 that govern ligand recognition and receptor activation are identified. Furthermore, molecular docking and functional assays reveal key factors that may define binding affinity and agonist potency of formyl peptides. These findings deepen our understanding about ligand recognition and selectivity mechanisms of the formyl peptide receptor family.

show abstract

“…More recently, LXA 4 was shown to activate bone regeneration in a pig model of periodontitis (Van Dyke et al , ) and to induce proliferation and migration of human periodontal stem cells (Cianci et al , ). Additionally, LXA 4 might play a role in modulating salivary gland inflammation by inhibiting immune cell binding to salivary epithelial cells (Chinthamani et al , ).…”

Section: Lipid Mediators Involved In Inflammationmentioning

confidence: 99%

Regulation of inflammation by lipid mediators in oral diseases

Sommakia

Baker

2016

Oral Diseases

View full text Add to dashboard Cite

Lipid mediators (LM) of inflammation are a class of compounds derived from ω-3 and ω-6 fatty acids that play a wide role in modulating inflammatory responses. Some LM possess pro-inflammatory properties, while others possess pro-resolving characteristics, and the class switch from pro-inflammatory to pro-resolving is crucial for tissue homeostasis. In this article, we review the major classes of LM, focusing on their biosynthesis and signaling pathways, and their role in systemic and, especially, oral health and disease. We discuss the detection of these LM in various body fluids, focusing on diagnostic and therapeutic applications. We also present data showing gender-related differences in salivary LM levels in healthy controls, leading to a hypothesis on the etiology of inflammatory diseases, particularly, Sjögren’s Syndrome. We conclude by enumerating open areas of research where further investigation of LM is likely to result in therapeutic and diagnostic advances.

show abstract

Lipoxin A₄ inhibits immune cell binding to salivary epithelium and vascular endothelium

Cited by 29 publications

References 95 publications

Supernatants and lipids from stored red blood cells activate pulmonary microvascular endothelium through the BLT2 receptor and protein kinase C activation

Supernatants and lipids from stored red blood cells activate pulmonary microvascular endothelium through the BLT2 receptor and protein kinase C activation

Structural basis of ligand binding modes at the human formyl peptide receptor 2

Regulation of inflammation by lipid mediators in oral diseases

Contact Info

Product

Resources

About

Lipoxin A4 inhibits immune cell binding to salivary epithelium and vascular endothelium

Cited by 29 publications

References 95 publications

Supernatants and lipids from stored red blood cells activate pulmonary microvascular endothelium through the BLT2 receptor and protein kinase C activation

Supernatants and lipids from stored red blood cells activate pulmonary microvascular endothelium through the BLT2 receptor and protein kinase C activation

Structural basis of ligand binding modes at the human formyl peptide receptor 2

Regulation of inflammation by lipid mediators in oral diseases

Contact Info

Product

Resources

About

Lipoxin A₄ inhibits immune cell binding to salivary epithelium and vascular endothelium