The motile response of lung macrophages: theoretical and experimental approaches using the linear under-agarose assay.

The alveolar macrophage plays an important role in the lung's defense against inhaled particles, but few studies have addressed the motile behavior of these cells. In this study, we measured alveolar macrophage random motility using a modification of the under-agarose assay. The cells were exposed to a uniform concentration of F-norleucyl-leucyl-phenylalanine (FNLLP) in an agarose system, establishing conditions for stimulated random motility (or chemokinesis). Experimental results were compared with a theoretical model of cell migration. In this model, chemokinesis was expressed as a random motility coefficient, mu, which is the cellular equivalent of a diffusion coefficient for a molecule. The experimental data that described the migration of alveolar macrophages (density profiles) agreed well with the theoretical model. The random motility coefficient ranged from 1 X 10(-9) cm2/sec (no FNLLP) to a maximum of 1 X 10(-8) cm2/sec at 10(-9) M FNLLP. For concentrations of FNLLP greater than 10(-9) M, the random motility decreased to a constant value of 3 X 10(-9) cm2/sec. The maximum random motility response was observed at an FNLLP concentration one order of magnitude below the measured FNLLP equilibrium dissociation constant, Kd, of 6 X 10(-8) M for alveolar macrophages and was essentially constant over a large range of FNLLP concentrations on either side of the Kd value. These results suggest that such a combined experimental and theoretical approach reduces the limitation of previous techniques that depended largely on physical characteristics of the assay and more closely identifies and measures intrinsic properties of cell motility.