Leukocytes Migrate through Three-Dimensional Gels of Midcycle Cervical Mucus

Abstract

The migration of leukocytes through mucus must be an essential factor in the mucosal immune response, particularly during mucosal invasion by pathogens. We used two methods to evaluate the ability of neutrophils to migrate through human midcycle cervical mucus: (i) direct visualization of cell migration within freshly collected mucus samples and (ii) quantification of cell penetration through a layer of mucus overlying a monolayer of cultured intestinal epithelial cells from the T84 cell line. Neutrophils migrated rapidly through human midcycle cervical mucus: the random motility coefficient (μ) ranged from 1.2 to 5.6 x 10 -8 cm 2/sec in different mucus samples. The rate and pattern of neutrophil migration in cervical mucus were identical to those in a structurally similar collagen gel (0.4 mg/ml). Therefore, we also quantitatively examined the migratory behavior of human neutrophils, monocytes, and lymphocytes from peripheral blood, as well as leukocytes isolated from semen, in collagen gels as a model of cell migration in cervical mucus. In the absence of stimulation, μ was ∼ 10 -8 cm 2/s for neutrophils and lymphocytes; monocytes and seminal leukocytes were immotile. In all cases, μ increased with the addition of FMLP. Furthermore, neutrophils were able to penetrate layers of mucus overlying monolayers of T84 cells when the gel thickness was less than ∼ 500 μm. These results suggest that leukocytes migrate effectively through mucus, a process which may be related to their ability to function in the mucosal immune system or to serve as vectors for the translocation of infectious pathogens like HIV.