Overexpression of sICAM-1 in the alveolar epithelial space results in an exaggerated inflammatory response and early death in XXXX .

@entity32 @entity55 @entity19 @entity3274 @entity358 @entity8024
BACKGROUND: A sizeable body of data demonstrates that membrane @entity8024 ( @entity8024 ) plays a significant role in host defense in a site-specific fashion. On the pulmonary vascular endothelium, @entity8024 is necessary for normal leukocyte recruitment during acute @entity32 . On alveolar epithelial cells (AECs), we have shown previously that the presence of normal @entity8024 is essential for optimal alveolar macrophage (AM) function. We have also shown that @entity8024 is present in the alveolar space as a soluble protein that is likely produced through cleavage of @entity8024 (sICAM-1) is abundantly present in the alveolar lining fluid of the normal lung and could be generated by proteolytic cleavage of @entity8024 , which is highly expressed on type I AECs. Although a growing body of data suggesting that intravascular sICAM-1 has functional effects, little is known about sICAM-1 in the alveolus. We hypothesized that sICAM-1 in the alveolar space modulates the innate immune response and alters the response to @entity358 . METHODS: Using the surfactant protein C (SPC) promoter, we developed a transgenic @entity19 (SPC-sICAM-1) that constitutively overexpresses sICAM-1 in the distal lung, and compared the responses of wild-type and SPC-sICAM-1 @entity19 following intranasal inoculation with @entity3274 . RESULTS: SPC-sICAM-1 @entity19 demonstrated increased mortality and increased systemic dissemination of organisms compared with wild-type @entity19 . We also found that inflammatory responses were significantly increased in SPC-sICAM-1 @entity19 compared with wild-type @entity19 but there were no difference in lung CFU between groups. CONCLUSIONS: We conclude that alveolar sICAM-1 modulates @entity55 . Manipulating @entity8024 interactions therapeutically may modulate the host response to Gram negative @entity358 .
