Interaction between chemoattractants and bacterial lipopolysaccharide in the induction and enhancement of neutrophil adhesion.
Chemotactic peptides in the circulation stimulate neutrophils to become sequestered in the pulmonary vasculature, and low concentrations of bacterial lipopolysaccharide (LPS) enhance and prolong this effect. This interaction of neutrophils with the vascular endothelium is thought to involve, in part, the increase in adhesiveness induced in neutrophils by such stimuli. In this study, the binding of albumin-coated latex beads to neutrophils was used to determine whether the enhancement seen with LPS results from an increase in the number of adhesive cells, from the enhancement of the adhesiveness of individual neutrophils, or both. Chemotactic peptides alone and LPS alone induced an increase both in the adhesive population and in the number of beads bound per individual neutrophil. The number of beads bound per cell increased over a very wide range of stimulus concentrations, showing that the degree of adhesiveness of an individual cell in the population varies over a considerable range. Trace concentrations of LPS (10 ng/ml or less), i.e., levels close to those measurable in vivo, had little effect on the proportion of neutrophils that were stimulated by chemotactic factor to become adhesive but did significantly enhance the number of beads bound to each individual neutrophil. The enhancement may require the presence of the CD11/18 glycoprotein complex, but was not further upregulated by LPS. No evidence could be obtained to suggest that the effect of LPS involved release of tumor necrosis factor (TNF) from the numbers of monocytes in the preparation, and the observations are consistent with a direct effect of LPS on the neutrophils. It is suggested that this increase in adhesive sites on the cell could explain the persistence of the sequestration of neutrophils in the microvasculature seen in the presence of both chemoattractants and LPS by enhancing the "strength" of the adhesion to endothelial cells. The increased adhesion may also set the stage for enhanced endothelial injury.
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
S K
SK
Young
G S
GS
Worthen
C
C
Haslett
M G
MG
Tonnesen
P M
PM
Henson
D015703:Antigens, CD / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects*; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte; D004926:Escherichia coli / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D016209:Interleukin-8; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016177:Macrophage-1 Antigen; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000648:ultrastructure; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D002630:Chemotactic Factors; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D016028:Receptors, Leukocyte-Adhesion; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D009240:N-Formylmethionine Leucyl-Phenylalanine