Smoking isn't the only threat to human lungs. Those delicate organsof breathing also suffer damage from infections, radiation (fromtherapy), adult and infant respiratory distress syndrome, inhalation oftoxins and impurities, oxygen free radicals and surfactant protein Bdeficiency, to name some of the main insults to lung tissue.When injured lungs switch on their tissue repair mechanism, or whenmodern medicine administers treatment, such as forced ventilation,the cure can be as harmful as the cause. Currently, there is notreatment for most forms of lung injury beyond supportive care tohelp the lung heal on its own.Lungs consist mainly of alveoli, thin-film epithelial tissue. These inturn consist mostly of empty space. Alveoli are microscopic sacs thatswap the blood's incoming oxygen for outgoing carbon dioxide. (Anaverage person's alveoli, if spread out, would cover a tennis court.)The alveolar epithelium consists of two cell types, alveolar types Iand II. Type II are progenitor or stem cells. When triggered by aninjury, they differentiate into the missing or wounded type I cells.Pulmonologist Jeffrey Whitsett, of Children's Hospital MedicalCenter, in Cincinnati, described last week how the lung's efforts tomend damage can result in chronic disease. He told journalistscovering the 95th annual Experimental Biology meeting, in Atlantalast week, that ventilation and other therapeutic procedures essentialto deal with the initial pulmonary insult may speed up the body's ownrepair process abnormally.Crippled Lung FormationWhitsett was previewing for the press one of the meeting's 514sessions, a symposium on "The role of growth factors in pulmonaryinjury and repair." At that briefing, he reported on two breeds oftransgenic mouse. One lacked the gene expressing a functionalreceptor for keratinocyte growth factor (KGF), which causes type IIalveolar cells to initiate pulmonary tissue repair.These mice died in utero or at birth because their lungs failed toform. Conversely, the other altered strain over-produced KGF in typeII cells, causing excessive production of lung tissue, and formingcysts within the lungs. These too died in utero."Scientifically, Whitsett's findings correlate very well with ours,"said Pulmonologist Ralph Panos, of Northwestern University inEvanston, Ill, who also addressed the Symposium. "They providevery strong evidence," Panos told BioWorld Today, "thatkeratinocyte growth factor is important in normal lung development."What we have shown," he added, "is that instillation of KGF via thetrachea stimulates proliferation of alveolar type II cells." He allowedrats that had inhaled the KGF to breathe only 100 percent oxygen.This exposed them to lung injury by oxygen free radicals. "Wefound," Panos said, "that with KGF treatment, 80 percent of theanimals could survive for about 120 hours." Untreated rats diedbetween 60 and 80 hours of exposure to the pure but toxic oxygen."Next," Panos said, "we will try other models of lung injury, and seeif the protein is effective there also." His ultimate aim is to see KGFdeveloped as a drug, "to promote lung repair after various forms ofinjury, such as adult respiratory distress syndrome."Amgen Endeavors To Put KGF Into ClinicPanos obtained his human, recombinant, E.-coli-derived KGF fromAmgen Inc., of Thousand Oaks, Calif., which is giving financial andmaterial support to academic researchers of the protein, includingWhitsett as well. The company, Developmental Biologist ScottSimonet told BioWorld Today, is investigating this growth factorunder license from the National Cancer Institute.Besides pulmonary injury, Simonet said that Amgen is pursuingkeratinocyte growth factor tissue-specific promoters that express ingastrointestinal or mammary or liver epithelium. "We will try tofind," said the scientist, "if there is some indication that mightwarrant taking KGF into the clinic, whether it might prove useful in atherapeutic setting. At the moment, we're too far away from knowingthat." n

-- David N. Leff Science Editor

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