Increased fibronectin mRNA in alveolar macrophages following in vivo hyperoxia.
Oxygen-mediated lung injury can stimulate a fibroproliferative response resulting in the alteration of the pulmonary extracellular matrix and subsequent scarring of parenchymal tissue. Fibronectin (FN), a component of the extracellular matrix, appears in increased quantities in fibrotic lung disease. Alveolar macrophages (AMs) are a potential source of this molecule. Using quantitative in situ hybridization, we demonstrated that AMs from rabbits acutely exposed to 100% oxygen (hyperoxia) for up to 64 h have 20-fold greater levels of FN mRNA relative to cells from control animals. When animals were allowed to recover in room air for up to 72 h after maximal oxygen exposure, AM FN mRNA abundance approached baseline levels. Furthermore, in oxygen-exposed animals, the fraction of lavaged cells expressing FN mRNA was increased 10-fold relative to controls. Although there was marked cell-to-cell variation, we conclude that the AM is a potential source of FN in the events leading to hyperoxia-induced pulmonary fibrosis.
Sinkin
R A
RA
Department of Pediatrics (Neonatology), University of Rochester, NY 14642.
LoMonaco
M B
MB
Finkelstein
J N
JN
Watkins
R H
RH
Cox
C
C
Horowitz
S
S
D000818:Animals; D015152:Blotting, Northern; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D005353:Fibronectins / Q000235:genetics*; D017403:In Situ Hybridization; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010100:Oxygen / Q000494:pharmacology*; D015347:RNA Probes; D012333:RNA, Messenger / Q000378:metabolism*; D011817:Rabbits
D005353:Fibronectins; D015347:RNA Probes; D012333:RNA, Messenger; D010100:Oxygen