Respiratory distress after intratracheal bleomycin: selective deficiency of surfactant proteins B and C.
Intratracheal bleomycin in rats is associated with respiratory distress of uncertain etiology. We investigated the expression of surfactant components in this model of lung injury. Maximum respiratory distress, determined by respiratory rate, occurred at 7 days, and surfactant dysfunction was confirmed by increased surface tension of the large-aggregate fraction of bronchoalveolar lavage (BAL). In injured animals, phospholipid content and composition were similar to those of controls, mature surfactant protein (SP) B was decreased 90%, and SP-A and SP-D contents were increased. In lung tissue, SP-B and SP-C mRNAs were decreased by 2 days and maximally at 4--7 days and recovered between 14 and 21 days after injury. Immunostaining of SP-B and proSP-C was decreased in type II epithelial cells but strong in macrophages. By electron microscopy, injured lungs had type II cells lacking lamellar bodies and macrophages with phagocytosed lamellar bodies. Surface activity of BAL phospholipids of injured animals was restored by addition of exogenous SP-B. We conclude that respiratory distress after bleomycin in rats results from surfactant dysfunction in part secondary to selective downregulation of SP-B and SP-C.
Savani
R C
RC
Division of Neonatology, Department of Pediatrics, The Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4399, USA. rsavani@mail.med.upenn.edu
Godinez
R I
RI
Godinez
M H
MH
Wentz
E
E
Zaman
A
A
Cui
Z
Z
Pooler
P M
PM
Guttentag
S H
SH
Beers
M F
MF
Gonzales
L W
LW
Ballard
P L
PL
D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D019084:Fluorescent Antibody Technique, Indirect; D007267:Injections; D008168:Lung / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D010743:Phospholipids / Q000032:analysis; D011510:Proteolipids / Q000494:pharmacology / Q000502:physiology; D011663:Pulmonary Surfactants / Q000172:deficiency* / Q000494:pharmacology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012131:Respiratory Insufficiency / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D014018:Tissue Distribution; D014132:Trachea
D010743:Phospholipids; D011510:Proteolipids; D011663:Pulmonary Surfactants; D001761:Bleomycin