Influence of synthetic polymers on neutrophil migration in three-dimensional collagen gels

Abstract

In vitro studies of cell migration within three-dimensional polymeric materials are essential for understanding cell behavior and for developing new biomedical materials. Human neutrophil motility was examined in hydrated collagen gels containing various synthetic polymers. Physical mixtures of collagen and certain water-soluble polymers formed stable gels that were good substrates for cell migration. Addition of either polyethylene glycol (PEG) or the pluronictrade mark copolymer F68 did not change the morphological or mechanical properties of collagen gels, as determined by SEM and oscillatory rheometry; however, addition of either polymer significantly inhibited cell motility in both a modified 96-well chemotaxis chamber assay and a direct visual assay. Although the mechanism for this observed polymer inhibition of neutrophil migration is not yet clear, these results suggest that PEG and F68, two widely used biomedical polymers that are considered to be relatively "inert," may cause significant inhibition of cell motility.

Effects of poloxamer 188 on human PMN cells

“…Low doses may prime/activate PMNs, similar to any other foreign substance, while higher doses may prevent activation. P188 has been previously shown to attenuate neutrophil adhesion and transendothelial migration in vivo 14, 16, 17 , prompting the hypothesis that P188 may interact with the cell membrane or adhesion molecule, acting as a competitive inhibitor of adhesion molecule interactions. The poloxamer may be acting in a similar fashion at very high doses in our study, preventing some level of NADPH independent activation by PMA and preventing interaction between the adhesion molecule and the antibody.…”

“…15 Tan and coworkers subsequently showed that neutrophil migration was inhibited by synthetic polymers in an in vitro , three-dimensional collagen gel. 14 Lane and colleagues followed their original work by assessing PMN migration in vivo after P188 treatment in a rodent model of bacterial sepsis. 16 They found a significantly increased mortality among rodents treated with P188 and attributed this to impaired neutrophil delivery to the inflammatory locus and a subsequent increased rate of sepsis.…”

“…10 P188 has also shown the ability to mitigate reperfusion injury after myocardial infarction 11, 12 and improve hemodynamics, and subsequent oxygen delivery, after hemorrhagic shock in humans. 13 Preliminary in vitro and animal model work has shown that P188 limits PMN migration 14, 15 , impairs PMN delivery to an inflammatory locus 16 , and attenuates enzyme release from PMNs. 17 Although these beneficial effects of P188 on PMNs have been previously seen, the direct effects of P188 on human PMNs are unknown.…”

Surfactant poloxamer 188—related decreases in inflammation and tissue damage after experimental brain injury in rats

“…Tan and Saltzman 43 reported that P-188 decreased neutrophil migration on a collagen matrix, as well as random cellular motion. The poloxamer, however, did not inhibit neutrophil migration in the absence of collagen.…”

“…22 Poloxamers have also been reported to have antiinflammatory effects in certain model systems. 30,43 Their antiinflammatory effect can derive from modulation of any of the following stages in the inflammatory process: 1) interference with intercellular adhesion molecule-mediated leukocyte margination; 2) modulation of the cytokine response; 3) modulation of chemotaxis; 4) blocking of opsonization; and 5) modulation of phagocytosis. The majority of studies involving the immunological effects of poloxamers have been focused on their effects on cell migration and phagocytosis.…”