EXPRESSION OF INTERCELLULAR-ADHESION MOLECULE-1 ON MACROPHAGES IN-VITRO AS A MARKER OF ACTIVATION

Macrophage activation is a major component of wound healing. It also d etermines the extent of inflammatory reactions and the response of the body to implanted materials. We have previously shown, using an in vi tro model, that the extent of spreading of macrophages on different ma terials is a marker of activation, and that a soluble inducer has a do se-response effect on the secretion of cytokines in the culture medium . This work investigates the expression of three different cell surfac e markers [macrophages MAC-1, MAC-3 and intercellular adhesion molecul e-1 (ICAM-1)] on macrophages in vitro using confocal microscopy and sh ows that ICAM-1 is also a marker of macrophage activation in this mode l. We observed increased amounts of ICAM-1 on activated macrophages co mpared to unactivated macrophages, whereas MAC-1 and MAC-3 were either expressed constitutively or demonstrated no quantitative change in ex pression after activation under the same experimental conditions. We a lso tested the expression of ICAM-1 with various concentrations of sol uble inducers (lipopolysaccharide, 0.001, 0.01, 0.1, 1 and 10 mu g ml( -1); S-27609, 0.1, 0.25, 0.5, 1, 2 and 3 mu g ml(-1)) and on a sheet o f polylactic acid alone or in combination with soluble inducers. All d oses of soluble inducers induced the expression of ICAM-1 on cells gro wn in glass chamber slides. The induction was not dose related but see med to work rather in an on-off manner. There was no effect of materia l on ICAM-1 expression on the cell surface when no soluble inducer was added. This was similar to cytokine secretion, which was not induced by our material alone. When either lipopolysaccharide or S-27609 was u sed in combination with the material, there was an increase in the ave rage measured intensity of ICAM-1. In this in vitro model, ICAM-1 stai ning as measured by confocal microscopy is a marker for macrophage act ivation. Our results suggest that the extent of macrophage activation as measured by ICAM-1 and by cytokine secretion is more sensitive to s oluble inducers than to the action of the flat sheet of polylactic aci d. (C) 1997 Elsevier Science Limited. All rights reserved.