Differing patterns of P-selectin expression in lung injury.
Using two models of acute lung inflammatory injury in rats (intrapulmonary deposition of immunoglobulin G immune complexes and systemic activation of complement after infusion of purified cobra venom factor), we have analyzed the requirements and patterns for upregulation of lung vascular P-selectin. In the immune complex model, upregulation of P-selectin was defined by Northern and Western blot analysis of lung homogenates, by immunostaining of lung tissue, and by vascular fixation of 125I-labeled anti-P-selectin. P-selectin protein was detected by 1 hour (long before detection of mRNA) and expression was sustained for the next 7 hours, in striking contrast to the pattern of P-selectin expression in the cobra venom factor model, in which upregulation was very transient (within the 1st hour). In the immune complex model, injury and neutrophil accumulation were P-selectin dependent. Upregulation of P-selectin was dependent on an intact complement system, and the presence of blood neutrophils was susceptible to the antioxidant dimethyl sulfoxide and required C5a but not tumor necrosis factor alpha. In contrast, in the cobra venom factor model, upregulation of P-selectin, which is C5a dependent, was also dimethyl sulfoxide sensitive but neutrophil independent. Different mechanisms that may explain why upregulation of lung vascular P-selectin is either transient or sustained are discussed.
Bless
N M
NM
Department of Traumatology, University of Freiburg, Germany.
Tojo
S J
SJ
Kawarai
H
H
Natsume
Y
Y
Lentsch
A B
AB
Padgaonkar
V A
VA
Czermak
B J
BJ
Schmal
H
H
Friedl
H P
HP
Ward
P A
PA
D000818:Animals; D000936:Antigen-Antibody Complex / Q000008:administration & dosage; D015152:Blotting, Northern; D015153:Blotting, Western; D015936:Complement C5a / Q000172:deficiency / Q000494:pharmacology; D003169:Complement Inactivator Proteins / Q000633:toxicity; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004195:Disease Models, Animal; D004546:Elapid Venoms / Q000494:pharmacology; D007074:Immunoglobulin G / Q000008:administration & dosage; D008297:Male; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D000936:Antigen-Antibody Complex; D003169:Complement Inactivator Proteins; D004546:Elapid Venoms; D007074:Immunoglobulin G; D019007:P-Selectin; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C016310:cobra venom factor; D015936:Complement C5a; D004121:Dimethyl Sulfoxide