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Departments of 1 Internal Medicine and 2 Pathology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5300
Fibroblasts can contract collagen gels, a process
thought to be related to tissue remodeling. Because epithelial cells
are also involved in repair responses, we postulated that human
bronchial epithelial cells (HBECs) could cause contraction of collagen
gels. To evaluate this, HBECs were plated on the top of native type I
collagen gels and were incubated for 48 h. After this, the gels were
released and floated in LHC-9-RPMI 1640 for varying times, and gel size was measured with an image analyzer. HBECs caused a marked
contraction of the gels within 24 h; the area was reduced by 88 ± 4% (P < 0.01). The degree of gel
contraction was dependent on cell density; 12,500 cells/cm2 resulted in maximal
contraction, and half-maximal contraction occurred at 7,500 cells/cm2. Contraction varied
inversely with the collagen concentration (91 ± 1% with 0.5 mg/ml
collagen vs. 43 ± 5% with 1.5 mg/ml collagen). In contrast to
fibroblasts that contract gels most efficiently when cast into the gel,
HBEC-mediated contraction was significantly (P < 0.01) more efficient when cells
were on top of the gels rather than when cast into the gels.
Anti-
1-integrin antibody
blocked HBEC-mediated contraction by >50%, whereas
anti-
2-,
anti-
3-, anti-
v-,
anti-
v
5-,
anti-
2-, or
anti-
4-integrin antibody was without effect. The combination of
anti-
1-integrin antibody and an
anti-
-subfamily antibody completely blocked gel contraction induced
by HBECs. In contrast, anti-cellular fibronectin antibody did not block
HBEC-induced gel contraction, whereas it did block fibroblast-mediated
gel contraction. In summary, human airway epithelial cells can contract
type I collagen gels, a process that appears to require integrins but
may not require fibronectin. This process may contribute to airway
remodeling.
integrin; repair; remodeling
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