Crawling-like movements, adhesion to solid substrata and chemokinesis of neutrophil granulocytes.
We analysed the chemokinetic actions of fMet-Leu-Phe (FMLP) and human serum albumin (HSA) on preparations of human neutrophils. Our work focused on the extent to which these agents, individually or in combination, affected locomotion by inducing changes in motile activity and/or the degree of cellular adhesion to the substratum. Because polymorphonuclear leucocyte (PMN) preparations derived from different individuals were found to exhibit broad variations in their basal motility and level of adhesiveness to glass substrata, it became of major interest to clarify mechanisms responsible for the reported variations in neutrophil responses to FMLP. We performed detailed studies on three separate PMN preparations, which differed in terms of their basal motility and adhesiveness. The unequivocal findings that emerged from this study were as follows: (1) HSA did not stimulate or modify motility of cells in suspension. Its orthokinetic effect was exclusively due to its capacity to decrease adhesion to the substratum. It prevented immobilization of motile cells that made contact with the substratum. (2) The orthokinetic effect of FMLP was primarily due to its effects on motility, but there were also secondary effects on spreading and adhesion. The peak chemokinetic activity of FMLP occurred at 10(-8)M, when measured by the two-filter count method and this was correlated with the percentage of polarized neutrophils in suspension. (3) The response to HSA and/or FMLP depended on the basal activity of the cells. If the cells were non-motile and spherical, HSA had no chemokinetic effect. Such an effect was only observed with cells that were initially motile. In contrast, the stimulatory effect of FMLP on motility and locomotion was marked in cases where basal motile activity of the neutrophils was low. If the basal motile activity was high, motility and locomotion could not be stimulated further. Therefore, the chemokinetic effects of HSA and FMLP can be predicted when one knows the basal motile activity of the neutrophils. The variable effect of FMLP on adhesion may also contribute to the regulation of locomotion. These findings help to explain earlier conflicting reports on the chemokinetic effect of FMLP. (4) FMLP can elicit simultaneous changes in motility and adhesiveness, which may have synergistic or antagonistic effects on locomotion. (5) The average speed of the whole neutrophil population is essentially regulated by changes in the proportion of locomoting cells and not, or to a lesser extent, by changes in the speed of the locomoting subset.(ABSTRACT TRUNCATED AT 250 WORDS)
D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008214:Lymphocytes / Q000502:physiology; D009000:Monocytes / Q000502:physiology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000502:physiology*; D012709:Serum Albumin / Q000494:pharmacology
D012709:Serum Albumin; D009240:N-Formylmethionine Leucyl-Phenylalanine