Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activity of the dipeptidyl hydrolase angiotensin-converting enzyme has been observed to be altered by treatment with bleomycin. We used an animal model of bleomycin lung toxicity to study the effects on angiotensin-converting enzyme activity in various lung fractions. Serum activity of angiotensin-converting enzyme increased only 23% after a single intratracheal instillation of bleomycin. Lung tissue angiotensin-converting enzyme activity fell to 40% of control level (p < 0.05) and returned toward and eventually exceeded control values during the ensuing 6 weeks. However, angiotensin-converting enzyme activity in alveolar lavage fluid from bleomycin-treated rats was elevated 30-fold above the barely detectable levels found in control animals. Angiotensin-converting enzyme activity in lavage fluid was soluble and was not associated with the alveolar cell pellet. Maximum elevation of lavage angiotensin-converting enzyme activity occurred 3 days following bleomycin instillation. Significant transudation of serum into alveolar lavage fluid occurred in bleomycin-treated rats. Nevertheless, this phenomenon would not explain the high levels of angiotensin-converting enzyme activity found in lavage fluid. Elevated lavage angiotensin-converting enzyme levels were detected after doses of bleomycin too low to cause significant sequelae of pulmonary fibrosis. Lavage angiotensin-converting enzyme is a sensitive monitor of tissue response to bleomycin.
 ...
PMID:Assessment of bleomycin lung toxicity using angiotensin-converting enzyme in pulmonary lavage. 615 67

Hapten immune pulmonary interstitial fibrosis (HIPIF) is induced by a recall cell-mediated immune response against the hapten 2,4, 6-trinitrobenzene sulphonic acid (TNBS) in the lung. Studies here dissect the role of the cellular components of the bronchoalveolar lavage (BAL) cells (alveolar macrophages [AMs] versus monocytes and immature dendritic cells) in the fibrogenic inflammatory response. BAL cells from HIPIF mice were generally more activated and produced a greater amount of tumour necrosis factor-alpha (TNF-alpha) than controls. Liposome-encapsulated dichloromethylene diphosphonate (Cl(2)MDP) that was inoculated intranasally (i.n.) into mice selectively depleted AMs. Following AM depletion, the number of TNF-alpha-containing cells was reduced, and both the number of immune inflammatory cells recruited into the alveolar space and the subsequent collagen deposition (hydroxyproline) were decreased in the sensitized and intratracheally (i.t.) challenged mice. In conclusion, AMs are required, in part, for the development of pulmonary fibrosis in HIPIF because AM-derived factors such as TNF-alpha are needed for initiation of chemokine and cytokine pathways and accumulation of immune inflammatory cells.
 ...
PMID:A critical role for alveolar macrophages in elicitation of pulmonary immune fibrosis. 1112 54