Biomedical Engineering Reference
In-Depth Information
cell in this process. Under normal conditions, the role of the neutrophil as a i rst
line of defense is to kill and eliminate endogenous and exogenous stimuli such
as airborne pollutants, allergens, and microbes by a variety of mechanisms (i.e.,
phagocytosis, respiratory burst, the release of cytotoxic mediators and proteases).
However, many bacterial infections and a variety of human diseases in their active
stages are characterized by the migration of neutrophils across epithelial surfaces.
h us, the transmigration of neutrophils across epithelial surfaces represents a
shared phenomenon among a diverse array of inl ammatory mucosal conditions.
For instance, salmonellosis, shigellosis, and pneumonia, as well as autoimmune/
idiopathic states such as Crohn's disease, ulcerative colitis, and bronchitis all
culminate in the destructive breach of the protective outer epithelium by activated
PMNs. Furthermore, the severity and clinical outcome of these inl ammatory
diseases correlate with the extent of PMN ini ltration.
Expanding the knowledge base of the adhesion molecules involved in the process
of neutrophil recruitment will ultimately lead to new targets for pharmacological
intervention. h e initial work in this regard has been encouraging, as several
therapeutic manipulations of the adhesion and migratory processes have been
successful in animal models. Furthermore, developmental endothelial locus
(Del)-1 has recently been reported to be an anti-adhesive factor that interferes
with LFA-1-dependent leukocyte-endothelial adhesion, and thus could provide a
basis for targeting leukocyte-endothelial interactions in disease (Choi
et al.
2008).
However, further development is required before such studies can translate and be
maximally ef ective in humans.
SUMMARY
• h e primary objective of neutrophils as i rst responders is to phagocytose
and destroy pathogenic microorganisms.
• Neutrophils represent an important ef ector of the acute (and chronic)
inl ammatory response.
• A common feature underlying active states of inl ammation is the migration
of neutrophils from the circulation and across a number of tissue barriers
in response to pathogenic insult or injury.
• A complex series of neutrophil adhesive and de-adhesive events with both
the endothelium and epithelium allows for successful migration.
• As the endothelium and epithelium of er potential direct targets for therapy,
a better understanding of such adhesive interactions with neutrophils will
lead to the discovery of novel anti-inl ammatory drugs.
