|Smith, C wayne|
Submitted to: Tissue Engineering
Publication Type: Peer reviewed journal
Publication Acceptance Date: 4/1/2004
Publication Date: 11/1/2004
Citation: Gonzalez, A.L., Gobin, A.S., West, J.L., McIntire, L.V., Smith, C.W. 2004. Integrin interactions with immobilized peptides in polyethylene glycol diacrylate hydrogels. Tissue Engineering. 10:1775-1786. Interpretive Summary: There is evidence that innate immunity requires that white blood cells adhere to the lining of blood vessels at sites of infection. We are attempting to define the specific molecules that allow this process to occur efficiently. In collaboration with bioengineers, we have studied the adhesion of white blood cells to artificial surfaces with specifically bound molecules that are known to occur on the surface lining of blood vessels. This new model allows study of individual molecules one at a time
Technical Abstract: This study employs tissue engineering technologies to evaluate neutrophil interactions with the extracellular matrix (ECM). We have used a polyethylene glycol (PEG) diacrylate derivative to form a hydrogel as a biologically inert surface. Covalently attaching bioactive moieties into the hydrogel has made it bioactive. The goal is to define the mechanisms by which these moieties influence the interactions of neutrophils with this bioactive hydrogel, and thus understand the likely effects of similar ligands in the ECM. The current experiments analyze the interactions of isolated human neutrophils with PEG hydrogels modified with Arg-Gly-Asp-Ser (RGDS), known ligand for some ß1 and ß3 integrins, and Thr-Mer-Lys-Ile-Ile-Pro-Phe-Asn-Arg-Leu-Thr-Ile-Gly-Gly (TMKIIPFNRLTIGG), ligand for Mac-1, a ß2 integrin. Our results demonstrate that neutrophils, independent of chemotactic stimulation, show little ability to adhere to unmodified PEG hydrogels. However, cell adhesion and spreading are robust on peptide-modified hydrogels. Incorporating distinct bioactive peptides, either alone or in combination, has enabled recognition of differential functions of 'vß3, ß1 and ß2 integrins on neutrophil adhesion and spreading. Combined interactions result in activity that differs markedly from that seen with either integrin independently engaged. This model allows investigation of specific ligand-induced leukocyte functions and the development of engineered matrices with defined bioactive properties.