MEDIATORS, CYTOKINES, AND GROWTH FACTORS IN LIVER-LUNG INTERACTIONS
Section snippets
INHERITED METABOLIC DISORDERS: α1-ANTITRYPSIN DEFICIENCY
α1-Antitrypsin (α1-AT) is a 52-kD protein that is a member of the serpin (serine proteinase inhibitor) family of antiproteinases.14, 79 It inhibits numerous proteases within the lung, including elastase, trypsin, chymotrypsin, and collagenases. α1-AT is produced by hepatocytes and is found in the serum and in bronchoalveolar lavage fluid. The serum concentration of α1-AT is elevated in inflammatory states, pregnancy, burns, and in association with malignancy and smoking. The single α1-AT gene
HEPATOPULMONARY SYNDROME
HPS is an increasingly recognized constellation of three clinical and laboratory findings: (1) liver disease, (2) a widened alveolararterial (A-a) oxygen gradient, and (3) intraparenchymal pulmonary vascular dilations (reviewed in the article on the subject by Krawka in this issue and in references 100 and 102). Although the pathogenesis of the alterations within the pulmonary circulation is not known, increased production and secretion of vasodilatory by the liver, or impaired hepatic
SYSTEMIC INFLAMMATORY STATES
The systemic inflammatory response syndrome (SIRS) is a complex constellation of physiologic and hematologic alterations that occurs after many different insults, including bacterial or fungal sepsis, infections with other pathogens, pancreatitis, hemorrhagic shock, or infusion of various cytokines such as tumor necrosis factor.16 SIRS may be complicated by the development of multiorgan dysfunction syndrome (MODS), characterized by an inability to maintain systemic homeostasis because of
HEPATOCYTE GROWTH FACTOR/SCATTER FACTOR
For many years it, has been known that the mammalian liver is able to regenerate in a controlled fashion after partial hepatectomy or injury. After removal of as much as 70% of the rat liver, the organ is able to recover normal weight and function.75 The idea that a soluble circulating factor might play a role in liver regrowth arose when cross-circulation experiments demonstrated that blood from partially hepatectomized animals stimulated liver growth in parabiotic animals. Using cultured
CONCLUSION
Many mediators, cytokines, and growth factors have been implicated in the interactions between the liver and the lungs in inherited metabolic disorders, HPS, and systemic inflammatory states. α1-Antitrypsin is an antiprotease produced primarily within the liver and is extremely important in the maintenance of the balance between pulmonary proteases and antiproteases. Deficiency or dysfunction of this antiprotease causes the premature and accelerated development of emphysematous lung disease. α1
ACKNOWLEDGMENTS
The authors thank Sharon Barque and Betty Montiel for expert secretarial assistance.
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Address reprint requests to, Ralph J. Panos, MD, Pulmonary Division, Northwestern University Medical School, Room 777, Passavant Pavilion, 303 East Superior Street, Chicago, IL 60611-3053
This work is supported in part by funding from the Veterans Administration.
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From the Veterans Administration Lakeside Medical Center (RJP), and Pulmonary Division, Department of Medicine (RJP, SKB), Northwestern University Medical School, Chicago, Illinois