Related Experiment Videos
Thromboxane-induced neutrophil adhesion to pulmonary microvascular and aortic endothelium is regulated by CD18
M E Wiles1, R Welbourn, G Goldman
1Laboratory for Microvascular Research, Biological Science Center, Boston University, Massachusetts 02215.
Abstract:
Thromboxane (Tx) A2 generation and subsequent selective pulmonary sequestration of neutrophils (PMNs) is characteristic of several forms of the adult respiratory distress syndrome (ARDS). Therefore, we examined PMN-dependent adhesion to cultured pulmonary microvessel and aortic endothelium (EC) in response to U46,619 (Tx mimic). Nonstimulated PMNs were two fold more adherent to pulmonary microvessel EC than to aortic EC (P less than 0.01). PMN pretreatment with Tx mimic (10(-6) M) increased adhesion to both types of EC (P less than 0.01). The Tx mimic-induced adhesion was blocked by receptor antagonists to Tx (SQ29,548) and to leukotrienes (FPL55,712), and by the anti-CD18 mAb TS1/18 (P less than 0.01, all cases). Baseline PMN adhesion also was modulated by Tx, leukotrienes, and CD18, for both EC types. These results indicate pulmonary microvessel EC is intrinsically more adhesive for both nonstimulated and stimulated PMNs than aortic EC and that Tx mediates PMN-dependent adhesion by coupled interaction of Tx and LT receptors via CD18 activation.
Insights
Pulmonary microvessel endothelium shows higher neutrophil adhesion than aortic endothelium. Thromboxane A2 (TxA2) mediates this adhesion via coupled Tx and leukotriene receptor interactions involving CD18.
Area of Science:
- Cardiovascular Biology
- Pulmonary Medicine
- Immunology
Background:
- Neutrophil sequestration in the lungs is a hallmark of adult respiratory distress syndrome (ARDS).
- Thromboxane A2 (TxA2) plays a role in ARDS pathogenesis.
- Endothelial cells (EC) and neutrophils (PMNs) are key players in inflammatory responses.
Purpose of the Study:
- To investigate the differential adhesion of neutrophils to pulmonary microvessel EC versus aortic EC.
- To elucidate the role of Thromboxane A2 (TxA2) in mediating PMN adhesion to endothelium.
- To identify the specific receptors and molecules involved in TxA2-induced PMN-EC interactions.
Main Methods:
- Cultured pulmonary microvessel and aortic endothelial cells (EC) were used.
- Neutrophil (PMN) adhesion assays were performed with and without TxA2 mimic (U46,619).
- Receptor antagonists for TxA2 and leukotrienes, and anti-CD18 monoclonal antibody (mAb) TS1/18 were employed to block adhesion.
Main Results:
- Nonstimulated PMNs exhibited significantly higher adhesion to pulmonary microvessel EC compared to aortic EC.
- TxA2 mimic pretreatment markedly increased PMN adhesion to both EC types.
- TxA2 mimic-induced adhesion was effectively blocked by Tx receptor antagonists, leukotriene receptor antagonists, and the anti-CD18 mAb.
Conclusions:
- Pulmonary microvessel EC possesses intrinsic properties making it more adhesive to PMNs than aortic EC.
- TxA2 is a critical mediator of PMN-dependent adhesion to endothelium.
- PMN adhesion involves a coordinated interaction between TxA2 and leukotriene receptors, mediated through CD18 activation.