P-selectin is upregulated early in the course of hyperoxic lung injury in mice.
While treatment with supplemental oxygen is often essential in patients with lung disease, prolonged therapy may cause lung injury by itself. Although the mechanisms responsible for initiating hyperoxic lung damage almost certainly involve primary oxidative transformations, the possible contributions of inflammation to the tissue injury have been attracting increasing research activity. Increases in intercellular adhesion molecule-1 (ICAM-1) coincide with the inflammation, but in other models of inflammation transient adhesion mediated by members of the Selectin gene family was found to be essential before ICAM-1/beta 2 interactions could occur. We, therefore, wondered whether a similar sequence of initial transient adhesion followed by subsequent responses would be observed in hyperoxic lung inflammation. We, therefore, determined the effects of hyperoxia exposure on lung mRNA for P- and E-Selectin in mouse lungs. We found that there was no detectable mRNA for E-Selectin through 72 h of hyperoxia exposure by Northern blotting, but that mRNA for P-Selectin was detectable as early as 48 h after initiation of hyperoxia. To determine the location of P-Selectin upregulation we examined hyperoxia-exposed mouse lungs by in situ hybridization and found that the upregulation of P-Selectin at 48 h was localized to large muscularized vessels, at 72 h expression was detected in some medium size muscularized vessels, and at 96 h abundant expression was observed also on nonmuscularized small vessels. In conclusion, increases in mRNA for P-Selectin early in the course of hyperoxia exposure suggest that P-Selectin expression in hyperoxic lungs increases in parallel with upregulation of ICAM-1, leading to the accumulation of neutrophils in hyperoxic lungs, and that interventions targeting these two adhesion molecules may lead to a diminution in hyperoxic lung inflammation and lung injury.
Zeb
T
T
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Piedboeuf
B
B
Gamache
M
M
Langston
C
C
Welty
S E
SE
D000818:Animals; D017403:In Situ Hybridization; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010100:Oxygen / Q000633:toxicity*; D019007:P-Selectin / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*
D019007:P-Selectin; D012333:RNA, Messenger; D010100:Oxygen