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ECSOD inhibits PMN Chemotaxis by Preventing Oxidative Fragmentation of Collagen
Author(s) -
Fattman Cheryl L.,
Tobolewski Jacob M.,
Tan Roderick J.,
Petersen Steen V.,
Enghild Jan J.,
Oury Tim D.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1161-b
Subject(s) - chemotaxis , chemistry , fragmentation (computing) , inflammation , microbiology and biotechnology , receptor , biochemistry , immunology , biology , ecology
Previous studies have found that the antioxidant enzyme extracellular superoxide dismutase (ECSOD) can inhibit neutrophillic (PMN) inflammation in a number of lung injury models. Other studies have determined that type I collagen and collagen fragments are potent chemoattractants and activators of PMNs. Notably, ECSOD binds to type I collagen and protects it from oxidative fragmentation. We therefore hypothesized that oxidatively generated fragments of collagen may enhance PMN chemotaxis and that ECSOD would inhibit this effect by preventing oxidative collagen fragmentation. To test this hypothesis, PMN chemotaxis was monitored using a modified Boyden chamber in which PMNs placed in the upper chamber of a transwell plate are separated from a type I collagen‐coated lower chamber by a porous membrane. Generation of oxidants in the lower, collagen‐coated chamber increased the chemotaxis of PMNs through the transwell membranes. This chemotatic response was neutralized when oxidants were generated in the presence of ECSOD. Pretreatment of PMNs with blocking antibodies to two collagen receptors, discoidin domain receptor 1 (DDR1) and the integrin 1 receptor, inhibited chemotaxis of PMNs across the membrane in response to oxidatively fragmented collagen. In summary, these studies demonstrate that oxidative collagen fragmentation induces PMN chemotaxis and that this response can be inhibited in the presence of the antioxidant enzyme ECSOD. This effect may constitute a mechanism by which ECSOD mediates inflammation in vivo.