Rapid deformation of "passive" polymorphonuclear leukocytes: the effects of pentoxifylline

Abstract

Entry times for spherical (no pseudopods) polymorphonuclear leukocytes (PMNs) into a 4 microns micropipet have been measured as a function of pipet suction pressure (2,500-20,000 dyn/cm2) and concentration of the drug pentoxifylline (PTX, 0.1-10.0 mM). For control cells (0 mM PTX), entry rates (reciprocal entry times) increased almost linearly with increasing suction pressure, indicating a Newtonian-like behavior. With incubation in PTX solutions, entry rate vs. suction pressure became increasingly non-linear, suggesting a shear-thinning effect for the dissipative structure. At a given suction pressure the rate of entry showed a dose-dependent increase with increasing PTX concentration, the effect being most pronounced at high suction pressures (20,000 dyn/cm2). Also, with increasing PTX concentration two other effects were observed: i) there was a decreased incidence of cells that displayed pseudopodia, and ii) there was an increased incidence of cells forming hernias and an increased streaming of cell cytoplasm during aspiration. The first observation points to a down-regulation of the cell's functional ability to "activate" in response to surface/chemical stimuli, and the second indicates that both the cortical and cytoskeletal networks are weakened either by disruption and/or reduction in density of the protein polymers. These observations are in line with other recently published experiments which suggest that the rheological effects of pentoxifylline on PMNs may be associated with the state of actin.