Bleomycin-induced pulmonary injury in mice deficient in SPARC.
SPARC (secreted protein, acidic and rich in cysteine) is a component of the matrix that appears to regulate tissue remodeling. There is evidence that it accumulates in the lung in the setting of pulmonary injury and fibrosis, but direct evidence of its involvement is only now emerging. We therefore investigated the development of pulmonary fibrosis induced by bleomycin administered either intratracheally or intraperitoneally in mice deficient in SPARC. Bleomycin (0.15 U/mouse) given intratracheally induced significantly more pulmonary fibrosis in mice deficient in SPARC compared with that in wild-type control mice, with the mutant mice demonstrating greater neutrophil accumulation in the lung. However, in wild-type and SPARC-deficient mice given intraperitoneal bleomycin (0.8 U/injection x 5 injections over 14 days), the pattern and severity of pulmonary fibrosis, as well as the levels of leukocyte recruitment, were similar in both strains of mice. These findings suggest that the involvement of SPARC in pulmonary injury is likely to be complex, dependent on several factors including the type, duration, and intensity of the insult. Furthermore, increased neutrophil accumulation in the peritoneal cavity was also observed in SPARC-null mice after acute chemical peritonitis. Together, these data suggest a possible role for SPARC in the recruitment of neutrophils to sites of acute inflammation.
Savani
R C
RC
Division of Neonatology, Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Zhou
Z
Z
Arguiri
E
E
Wang
S
S
Vu
D
D
Howe
C C
CC
DeLisser
H M
HM
D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage / Q000633:toxicity*; D003094:Collagen / Q000032:analysis; D006909:Hydroxyproline / Q000032:analysis; D007274:Injections, Intraperitoneal; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology*; D015676:Osteonectin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*
D015676:Osteonectin; D001761:Bleomycin; D003094:Collagen; D006909:Hydroxyproline