Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.2.1.7 (BAL)
 1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulmonary sarcoidosis involves development of parenchymal granulomata that usually resolve spontaneously; however, it remains unclear what pathogenic mechanisms are responsible for the progression to local or diffuse fibrosis with irreversible lung remodeling that occurs in 20% of patients. Alveolar macrophages have a pivotal role in sarcoidosis, releasing mediators including insulin-like growth factor (IGF)-1, a potent profibrogenic molecule. IGF-1 bioavailability in the lung is dependent on at least six high-affinity IGF-binding proteins (IGFBP), which mainly inhibit IGF-1 action. We have investigated their presence in patients with established stage III sarcoidosis to determine whether IGF-1 and IGFBP contribute to the fibrogenic process in these patients and as such contribute to the (clinical) progression of the disease. The fibroblast mitogenic potential of bronchoalveolar lavage fluid (BALF) was more than 3-fold higher (P < 0.005) in sarcoid patients. Sarcoid BALF-induced activity could be inhibited (P < 0.0005) by neutralizing antibodies to IGF-1. We established the IGFBP profile of BALF with Western ligand analysis and quantified expression of IGFBP-3 by immunoblotting. IGFBP-2 and IGFBP-4 predominate in normal and sarcoid BALF, but IGFBP-3 occurs only as a modified, smaller, 29-kD form, expression of which was raised (P < 0.003) in sarcoid patients. Gene expression of IGF-1 and IGFBP-3 was demonstrated by reverse transcription-polymerase chain reaction in BAL cells. Thus, local production of pro-fibrogenic IGF-1 may be subject to substantial post-translational regulation by associated IGFBP and IGFBP proteases that may contribute to enhanced fibrogenesis in sarcoidosis patients with evidence of progression or (development) of fibrosis.
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PMID:Expression of insulin-like growth factor binding proteins in bronchoalveolar lavage fluid of patients with pulmonary sarcoidosis. 969 97

Bronchiolitis obliterans syndrome (BOS) is the major complication limiting survival of lung transplant recipients (Tx patients). The mechanisms underlying this fibrotic process are not known. We assessed IGF-1 and IGFBP-3 expression, critical mediators in different models of pulmonary fibrosis, in nine Tx patients. Three of them developed a BOS at 8, 14, and 17 mo postgraft, respectively. Two of the remaining six displayed a recurrent cytomegalovirus (CMV) infection, and four are in stable condition. IGF-1 mRNA expression was quantitated by RT-PCR in cells from four to six BAL per patient performed during the first 6 mo postgraft. Contrasting with a constantly low expression of IGF-1 mRNA in BAL cells from the six patients without BOS, the three patients with BOS presented marked peaks of IGF-1 on two to five occasions during the study period. These peaks, 3- to 13-fold increased compared with values from the former patients, preceded the diagnosis of BOS by 7, 13, and 17 mo, respectively. On the other hand, IGFBP-3 was highly and exclusively expressed in the three patients with BOS, the mRNA as well as the gene product as demonstrated by Western blotting. Our data strongly argue for a role of IGF-1 and IGFBP-3 in the fibrotic process underlying BOS, and for their possible value as an early marker of this complication.
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PMID:Insulinlike growth factor-1 in lung transplants with obliterative bronchiolitis. 1085 79