Expression of the β6 Integrin Subunit Is Associated with Sites of Neutrophil Influx in Lung Epithelium

Abstract

S U M M A R YInhalation of ozone by Rhesus monkeys results in epithelial injury and granulocyte influx in both conducting airways and respiratory bronchioles. We have reported that ozone-induced neutrophil recruitment and subsequent epithelial repair can be inhibited in vivo with a CD18 antibody. The antibody-mediated effect is abrogated by local instillation of C5a (a CD18-independent neutrophil chemoattractant), thereby demonstrating a role for neutrophils in lung epithelial repair processes. As an extension of this study, we examined the effect of ozone and neutrophil influx on epithelial expression of the ␤ 6 integrin, an adhesion molecule associated with proliferation and repair. Expression of ␤ 6 integrin was determined by immunohistochemistry for ozone-exposed monkeys treated with either control immunoglobulins or a CD18 antibody. The tracheal epithelium of ozoneexposed monkeys treated with control immunglobulins expressed the ␤ 6 integrin. In contrast, the tracheal epithelium of ozone-exposed monkeys treated with CD18 antibody exhibited very low to undetectable expression of ␤ 6 integrin. In association with C5a instillation and neutrophil influx, ␤ 6 integrin was also observed in respiratory bronchiolar epithelium from both control and ozone-exposed animals. These findings cumulatively suggest that lung epithelial cell expression of ␤ 6 integrin is associated with sites of neutrophil recruitment.

Distinct structural requirements for binding of the integrins αvβ6, αvβ3, αvβ5, α5β1 and α9β1 to osteopontin

“…In response to tissue injury or inflammation, avh6 is commonly highly induced (Hakkinen et al, 2004;Miller et al, 2001;Sawada et al, 2004). Osteopontin is also expressed at low levels in healthy adult organs, but dramatically induced in the setting of injury (Iguchi et al, 2004;Isoda et al, 2002;Takahashi et al, 2004;Wang et al, 2000).…”

Making sense of latent TGFβ activation

“…The expression of αvβ6 is restricted to epithelia, and in most epithelia the integrin is normally expressed at low levels (Breuss et al, 1993). In response to wounding or inflammation, the expression of αvβ6 increases (Breuss et al, 1995;Miller et al, 2001). Therefore, epithelial cell upregulation of αvβ6 and subsequent TGFβ activation is a situation in which the cellular response to a process (inflammation) produces a potent suppressor of that process.…”

Transforming Growth Factor-β: Master Regulator of the Respiratory System in Health and Disease

“…There are multiple mechanisms by which TGF-b can be released from this complex, including acidification, extremes of temperature, oxidation, proteolytic cleavage, and traction by integrins (6). Known activating molecules include matrix metalloproteinase (MMP)-2 and -9 (10), thrombospondin-1 (11,12), and integrins including a v b 6 (13,14). It is noteworthy that many of these activators are up-regulated after inflammation and/or wound healing, thus allowing increased TGF-b activation in the appropriate context.…”