Biomedical Engineering Reference
In-Depth Information
A model is proposed that integrates the role of CAMs in inl ammatory injury
and mononuclear cell transmigration through endothelium into injured tissue
sites in both I/R injury and DCS. In this model, tissue damage results from the
rapid release of reactive oxygen species, nitric oxide, inl ammatory cytokines from
injured endothelium as well as from blood mononculear cells. h ese molecules
induce upregulation of CAMs on endothelium and subsequent transmigration of
blood leukocytes into ischemic (hypoxic) site. h e role of adenosine and a specii c
tissue receptor for adenosine (A
2A
R) in mitigating the inl ammatory damage in
I/R injury and DCS is exciting and promises a strategy for intervention in these
pathological states.
INTRODUCTION
In this brief review, we examine the role of cell adhesion molecules (CAMs) in two
clinical entities characterized by tissue hypoxia: decompression sickness (DCS)
and the better understood ischemia-reperfusion (I/R) injury. DCS is also called
decompression syndrome, bends, or caisson disease. As dei ned by the Merriam-
Webster Medical Dictionary/Medline Plus, DCS is a sometimes fatal disorder that
is marked by neuralgic pains and paralysis, distress in breathing, and ot en collapse
that is caused by the release of gas bubbles (as of nitrogen) in tissue upon too rapid
decrease in air pressure at er a stay in a compressed atmosphere. h e restoration
of circulation at er a period of ischemia results in inl ammation and oxidative
damage through the induction of oxidative stress (Pacher
et al.
2008, Jang
et al.
2009). Nitric oxide (NO) produced during reperfusion reacts with superoxide
to produce the potent reactive species peroxynitrite (Pacher
et al.
2008). h ese
molecules and reactive oxygen species or ROS (molecular oxygen, superoxide and
hydroxyl radicals) attack cell membrane lipids, proteins, and glycosaminoglycans,
causing further damage (Pacher
et al.
2008, Jang
et al.
2009).
h e endothelium is intimately involved in a variety of pathologies including I/R
injury, DCS, inl ammation, oxidative stress, edema, thrombosis and hemorrhage.
In exploring the role of CAMs in DCS and I/R injury, we examined their
participation in inl ammatory tissue injury. Leukocytes arriving at the injured
areas release a plethora of inl ammatory mediators (interleukins, free radicals,
etc. (Pacher
et al.
2008, Jang
et al.
2009). h e reintroduction of oxygen into the
damaged sites initiates a cascade of reactions—damage to cellular proteins, DNA
and plasma membranes—which may then cause a release of more free radials and
cellular apoptosis. Leukocytes may collect in and damage small capillaries leading
to thrombi formation and ischemia.
CAMs AND TRANSMIGRATION
Expression of intercellular adhesion molecule 1 (ICAM-1) and vascular adhesion
molecule 1 (VCAM-1) on endothelial cells causes extravasation of T cells and
