Adhesion Molecules and Neutrophil Migration - Adhesion Molecules - page 140

neutrophils may be detrimental to the host. To this end, decay accelerating factor
(DAF, CD55) functions to clear neutrophils at the mucosal surface. DAF is a
complement regulatory protein that plays a crucial role in inhibiting complement-
mediated cell lysis and is highly expressed on the epithelial apical surface of at
least the lung and intestine. In addition, DAF most likely competes with ICAM-1
to dislodge neutrophils away from the epithelial surface (Louis et al. 2005). CD97
on neutrophils has also been shown to bind to DAF (Zemans et al. 2009).
ADHESION MOLECULES AND NEUTROPHIL
CHEMOATTRACTANTS
Recruitment of neutrophils across epithelial surfaces, such as the intestinal
epithelium, is dependent not only on specii c adhesion molecules but also on
neutrophil chemoattractants that dif use from the intestinal lumen (Figure 2) .
An intriguing and emerging concept is that neutrophils utilize distinct adhesion
molecules during transepithelial migration depending on the chemoattractant
gradient imposed. Early studies determined that many neutrophil chemoattractants
have the ability to modulate the expression of certain adhesion molecules. For
example, fMLP has been shown to cause an increase in the expression of CD18/
CD11b on the surface of neutrophils (Vedder and Harlan, 1988). More recently,
Blake et al. (2004) demonstrated that although neutrophil migration across T84 cell
monolayers in response to an imposed gradient of fMLP is dependent upon CD18/
CD11b, neutrophils are capable of migrating across T84 monolayers in a CD18-
independent manner in response to gradients of alternative chemoattractants
such as IL-8, complement component C5a, and leukotriene (LT)B 4 . Such
observations underscore a versatility by which neutrophils may utilize distinct
adhesion molecules depending on the chemoattractant gradient sensed during
transepithelial migration.
In support of this emergent view, our group has established a discreet role for
the neutrophil chemoattractant hepoxilin A 3 (HXA 3 ) in the process of neutrophil
recruitment (Pazos et al. 2008). HXA 3 is an eicosanoid derived from the 12-
lipoxygenase pathway, which is produced by epithelial cells and secreted from
the apical surface, resulting in the guidance of neutrophils across the epithelial
monolayer from the basolateral to the apical side. In studying the adhesion
molecules required for neutrophil transepithelial migration to imposed gradients of
HXA 3 , we found that the adhesion interaction proi le of neutrophil transepithelial
migration in response to HXA 3 dif ers from that exhibited by the structurally
related eicosanoid LTB 4 , suggesting that these neutrophil chemoattractants play
fundamentally dif erent roles in the recruitment process (Hurley et al. 2008).
Furthermore, unique to neutrophil transepithelial migration induced by gradients
of HXA 3 , but not LTB 4 or fMLP, was the critical dependency of four major surface
adhesion molecules (CD18, CD47, CD44, and CD55). While neutrophil migration