Differing Patterns of P-Selectin Expression in Lung Injury

• Published in: The American journal of pathology Vol. 153; no. 4; pp. 1113 - 1122
• Main Authors: Bless, Nicolas M., Tojo, Shinichiro J., Kawarai, Hiroko, Natsume, Yasuhiro, Lentsch, Alex B., Padgaonkar, Vaishalee A., Czermak, Boris J., Schmal, Hagen, Friedl, Hans P., Ward, Peter A.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.10.1998; ASIP; American Society for Investigative Pathology
• Subjects: Animals; Antigen-Antibody Complex - administration & dosage; Biological and medical sciences; Blotting, Northern; Blotting, Western; Complement C5a - deficiency; Complement C5a - pharmacology; Complement Inactivator Proteins - toxicity; Dimethyl Sulfoxide - pharmacology; Disease Models, Animal; Elapid Venoms - pharmacology; Immunoglobulin G - administration & dosage; Male; Medical sciences; P-Selectin - genetics; P-Selectin - metabolism; Pneumology; Pulmonary Alveoli - drug effects; Pulmonary Alveoli - metabolism; Pulmonary Alveoli - pathology; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - metabolism; Pulmonary Fibrosis - pathology; Rats; Rats, Long-Evans; Regular; Respiratory system : syndromes and miscellaneous diseases; RNA, Messenger - metabolism; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Up-Regulation; Immunohistochemistry; Rat; Pathogenesis; Lung; Activation; Complement; Deposition; Lung disease; Respiratory disease; Acute; Rodentia; Cell adhesion molecule; Inflammation; Adhesion; Northern blotting; P Selectin; Pathology; Vertebrata; Experimental disease; Mammalia; Animal; Venom; Molecular biology; Comparative study; Immune complex
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)65655-6

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 α. 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.