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In vivo selection of inflammation markers on leukocytes in ischemic hearts
Author(s) -
Schmidt M. O.,
Schober T.,
Wellstein A.,
Knollmann B. C.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.139
Subject(s) - inflammation , in vivo , ischemia , phage display , immunology , endothelium , chemotaxis , endothelial stem cell , cell adhesion molecule , medicine , biology , microbiology and biotechnology , in vitro , antibody , receptor , biochemistry , genetics
Loss of function of endothelial cells promotes an inflammation reaction, which induces the expression of inflammation‐specific surface proteins. Adhesion molecules and chemotactic factors mediate the entry of leukocytes into the artery wall. Here, we attempt to identify genes expressing cell surface markers involved in the reaction of endothelial cells to injury. For this purpose, we have generated a T7 phage display cDNA library from maturated bone marrow cells containing about 25% monocytes taken from healthy human donors. It has been shown previously that during myocardial ischemia‐reperfusion injury the myocardium and endothelium undergo an inflammatory‐like response. Thus, as a model we used Langendorff preparations of isolated mouse hearts that are subjected to ischemic stopped‐flow conditions followed by reperfusion. After several rounds of binding of the phage display library to ischemic and healthy hearts we successfully enriched for phages, which bind specifically to ischemic hearts. The selected phages have been isolated and several clones of both known and novel genes have been identified. Conclusion Identifying novel leukocyte inflammation markers as well as their binding partners on endothelial cells should provide insight into the mechanisms of interaction between leukocytes and endothelial cells during inflammation reactions. This might lead to the development of drugs preventing ischemic reperfusion injury. Clinical Pharmacology & Therapeutics (2005) 77 , P65–P65; doi: 10.1016/j.clpt.2004.12.139