Related Experiment Video
Updated: Feb 11, 2026
Polyelectrolyte Complex for Heparin Binding Domain Osteogenic Growth Factor Delivery
Published on: August 22, 2016
The role of β2 integrin associated heparin-binding protein release in ARDS
Yang Liu1, Shaolin Ma2, Xuebin Wang2
1Department of Critical Care Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Department of Critical Care Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China.
Aims:
PMNs (polymorphonuclear neutrophil) play important roles in early stage of inflammation induced ARDS (Acute Respiratory Distress Syndrome). Both HBP (Heparin-Binding Protein) released from active PMNs and β2 integrins on the surface of PMNs are involved in vascular leakage. The role and relationship of HBP and β2 integrins on ARDS still requires study.
Materials And Methods:
We established ARDS model using C57BL/6 mice with cecal ligation and puncture and eliminating HBP and β2 integrin with respective antibodies. The mice were also challenged with HBP endotracheal instillation. Histopathology score, lung wet/dry ratio, bronchoalveolar lavage fluid protein, plasma HBP and β2 integrin on PMNs from all groups were measured. β2 integrin and HBP were analyzed after incubated PMNs with streptococcal and pretreat with anti-CD18, anti-HBP, 1-phosphatidylinositol 3-kinase (PI3K) inhibitor and p38 mitogen-activated protein kinase (MAPK) inhibitor.
Key Findings:
All lung injury indicatrix accompanied with HBP and β2 integrin elevated in CLP group, and HBP and β2 integrin were in correlation with each other and both were in correlation with the severity of lung injury. Endotracheal instillation HBP induced lung injury in CLP mice. Inhibiting both HBP and integrin ameliorated lung injury. HBP release was suppressed by inhibiting integrin and PI3K pathway, while integrin level did not decrease after eliminating HBP.
Significance:
Both HBP and β2 integrin play important roles in ARDS. HBP released from PMNs is β2 integrin-PI3K signaling pathway dependent process revealing potential novel therapeutic targets for ARDS treatment.
Insights
Heparin-Binding Protein (HBP) and β2 integrin, both elevated in Acute Respiratory Distress Syndrome (ARDS), are crucial for vascular leakage. Targeting the β2 integrin-PI3K pathway offers a novel therapeutic strategy for ARDS.
Area of Science:
- Immunology
- Pulmonary Medicine
- Cell Biology
Background:
- Polymorphonuclear neutrophils (PMNs) are key players in early inflammation during Acute Respiratory Distress Syndrome (ARDS).
- Both Heparin-Binding Protein (HBP) released from activated PMNs and β2 integrins on PMN surfaces contribute to vascular leakage in ARDS.
- The precise relationship and roles of HBP and β2 integrins in ARDS pathogenesis require further elucidation.
Purpose of the Study:
- To investigate the roles and interrelationship of HBP and β2 integrins in the development of ARDS.
- To explore the potential of targeting HBP and β2 integrin pathways for ARDS treatment.
Main Methods:
- An ARDS mouse model was established using cecal ligation and puncture (CLP).
- Mice were treated with antibodies to inhibit HBP and β2 integrin, or challenged with HBP via endotracheal instillation.
- PMNs were analyzed in vitro following stimulation and pre-treatment with inhibitors of β2 integrin, HBP, PI3K, and MAPK pathways.
Main Results:
- The CLP group exhibited elevated levels of HBP and β2 integrin, which correlated with each other and the severity of lung injury.
- Endotracheal HBP instillation exacerbated lung injury in CLP mice.
- Inhibition of both HBP and β2 integrin ameliorated lung injury, with HBP release found to be dependent on the β2 integrin-PI3K pathway.
Conclusions:
- HBP and β2 integrin are critical mediators in ARDS pathogenesis.
- HBP release from PMNs is regulated by the β2 integrin-PI3K signaling pathway.
- This pathway represents a promising therapeutic target for ARDS treatment.
Related Concept Videos
01:10Integrins
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
01:15Activation of Integrins
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
01:28Role of Proteins in the Human Body
01:20Factors Affecting Protein-Drug Binding: Protein-Related Factors
The physicochemical properties of a drug play a significant role in its ability to bind to proteins. Lipophilic drugs, which dissolve in fats, oils, and lipids, can be...
02:18The Equilibrium Binding Constant and Binding Strength
01:29Drug Distribution: Plasma Protein Binding