B. Redl et al., IDENTIFICATION OF A LIPOCALIN IN MUCOSAL GLANDS OF THE HUMAN TRACHEOBRONCHIAL TREE AND ITS ENHANCED SECRETION IN CYSTIC-FIBROSIS, Laboratory investigation, 78(9), 1998, pp. 1121-1129
Citations number
37
Categorie Soggetti
Pathology,"Medical Laboratory Technology","Medicine, Research & Experimental
Members of the lipocalin protein family are characterized by their abi
lity to bind small hydrophobic molecules. Some of them are known to be
produced by various glands and secretory cells. Under certain conditi
ons, these proteins would be ideally suited for clearance of lipophili
c, potentially harmful substances and might also act as protection fac
tors in airway secretions. We therefore used RT-PCR analysis with a se
t of oligonucleotide primers deduced from conserved regions of lipocal
in members to identify specific RNA isolated from human trachea. With
two of these oligonucleotide primers, a positive result was obtained.
Sequencing of the RT-PCR products revealed that the DNA fragments were
identical to the lipocalin 1 (LCN1) encoding cDNA. LCN1 is an unusual
lipocalin member that binds a variety of lipophilic compounds and exh
ibits cysteine proteinase inhibitor and antimicrobial activities. The
local production and topographic distribution of LCN1 in the human tra
cheobronchial tree was then investigated by immunoperoxidase staining
on thin-layer sections using a specific antiserum. LCN1 was detectable
in the acini of serous mucosal glands and sometimes within the glandu
lar lumen, suggesting excretion of the protein. The latter finding was
tested and verified by Western blot analysis of bronchial secretions
of healthy individuals. Furthermore, the results of SDS-PAGE and Weste
rn blot analysis of bronchial secretions from patients with cystic fib
rosis (CF), which are usually characterized by an increase of airway l
ipids, suggested that LCN1 secretion was enhanced. Northern blot analy
sis of RNA from normal trachea and RNA isolated from tracheal biopsies
of patients with CF indicated that induced secretion was due to an up
-regulated expression of the LCN1 gene. Thus, our investigations prese
nt the first clear evidence that LCN1 is induced in infection or infla
mmation and support the idea that this lipocalin functions as a physio
logic protection factor of epithelia in vivo.