Activated human peripheral blood neutrophils produce epithelial injury and fibronectin breakdown in vitro.

Abstract:

:The ability of peripheral blood neutrophils to injure elements of the alveolar septum was assessed. Experiments consisted of activating previously isolated neutrophils (PMNs) with a soluble (phorbol myristate acetate, PMA) and a particulate (zymosan) trigger, and measuring detachment of 51Cr-labeled epithelial cells. In addition, the mechanisms of epithelial injury were investigated by including anti-proteinase and antioxidants in the system. Untriggered PMNs produced only slight detachment injury to epithelial cells at two effector-target cell ratios, this effect being dramatically increased after triggering with PMA; zymosan caused triggering but less than was produced by PMA. Alpha-1-protease inhibitor produced a decrease in detachment when both PMA- and zymosan-triggered cells were the effectors; superoxide dismutase did not significantly reduce detachment. The ability of triggered PMNs to cause proteolysis of fibronectin, as measured in a radiolabeled fibronectin matrix degradation assay, was related to their triggerability in the detachment assay, zymosan being largely ineffective in triggering enhanced proteolysis. These findings suggest that fibronectin is important in maintaining the integrity of the alveolar epithelial surfaces. Furthermore, in inflamed alveoli, activated PMNs can release proteinases, which cause degradation of this matrix component leading to compromise of the alveolar epithelial barrier.

journal_name

Inflammation

journal_title

Inflammation

authors

Brown DM,Brown GM,Macnee W,Donaldson K

doi

10.1007/BF00917512

keywords:

subject

Has Abstract

pub_date

1992-02-01 00:00:00

pages

21-30

issue

1

eissn

0360-3997

issn

1573-2576

journal_volume

16

pub_type

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