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TNF regulates leukocyte-endothelial cell interactions and microvascular dysfunction during immune complex-mediated
M Ursula Norman1, Karyn J Lister, Yuan H Yang
1Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, 246 Clayton Road, Clayton, Vic., 3168, Australia.
British Journal of Pharmacology
|January 19, 2005
Summary
Tumor necrosis factor (TNF) drives immune complex inflammation by increasing leukocyte interactions with blood vessels. Blocking TNF reduces these interactions and associated microvascular injury.
Area of Science:
- Immunology
- Inflammation research
- Vascular biology
Background:
- Immune complex deposition triggers inflammatory responses.
- Leukocyte-endothelial cell interactions are crucial in inflammation.
- The specific role of TNF in these processes requires direct assessment.
Purpose of the Study:
- To directly evaluate the role of TNF in immune complex-induced leukocyte-endothelial cell interactions.
- To investigate TNF's contribution to microvascular dysfunction during inflammation.
- To determine the impact of TNF on leukocyte recruitment and microvascular permeability.
Main Methods:
- Utilized intravital microscopy in wild-type and TNF knockout mice.
- Induced immune complex formation using the reverse passive Arthus (RPA) reaction in cremaster muscle.
- Quantified leukocyte rolling, adhesion, emigration, and microvascular permeability.
Main Results:
- Immune complex deposition increased leukocyte adhesion and emigration in wild-type mice.
- TNF knockout mice showed significantly reduced leukocyte adhesion, emigration, and rolling velocity changes.
- Reduced expression of P-selectin, E-selectin, and VCAM-1 was observed in TNF knockout mice.
- Microvascular permeability was attenuated in TNF knockout mice.
Conclusions:
- TNF plays a significant role in promoting leukocyte recruitment during immune complex-induced inflammation.
- TNF enhances leukocyte-endothelial interactions via increased expression of selectins and VCAM-1.
- TNF-mediated leukocyte recruitment directly correlates with increased microvascular injury.