title: Plasma from patients with sepsis up-regulates the expression of CD49d and CD64 on blood neutrophils.
abstract: An excessive interaction of blood neutrophils with microvascular walls may underlie the organ failure of sepsis. In this study, flow cytometric analysis was used to investigate whether plasma from 22 patients with sepsis altered the expression of the adhesion molecules (CD11a, CD11b, CD49d, and CD62L) on normal blood neutrophils and enhanced their binding to cultured endothelium. Most of the plasma samples from patients with sepsis increased the percentage of neutrophils bearing CD49d (86% samples versus 22% normal plasma samples; P < 0.001) and CD64 (69% samples versus 17% normal plasma samples; P < 0.001). This effect was not seen with plasma from patients with community-acquired infections who did not develop sepsis, nor with plasma from patients with acute or chronic inflammation who had no evidence of infection. A direct association was noted between the percentage of neutrophils expressing CD64 in the blood of patients with sepsis and the ability of plasma from these patients to up-regulate CD64 on normal neutrophils. Although CD62L was present on the majority of neutrophils after incubation with sepsis plasma, it was less apparent when the cells were cultured with normal plasma. The patients' plasma had no effect on neutrophils expressing CD11a and CD11b. High levels of TNF-alpha, IL-6, IL-8, and IL-10 were detected in the patients' blood, but incubation of the recombinant forms of these cytokines with neutrophils, even in the presence of LPS, did not increase CD49d and CD64 expression. The sepsis plasma also enhanced the attachment of neutrophils to untreated and TNF-alpha-treated endothelium, and this binding was impeded by anti-CD49d and anti-CD64 antibodies. We suggest that changes in the phenotype of neutrophils by circulating factors may facilitate their attachment to endothelium, which may be an important factor in the induction of organ dysfunction in severe sepsis.
authors.affiliation: Cardiovascular Division, King's College London, London, United Kingdom.
authors.forename: Sion M
authors.initials: SM
authors.lastname: Lewis
authors.forename: David F
authors.initials: DF
authors.lastname: Treacher
authors.forename: Lesley
authors.initials: L
authors.lastname: Bergmeier
authors.forename: Susan D
authors.initials: SD
authors.lastname: Brain
authors.forename: David J
authors.initials: DJ
authors.lastname: Chambers
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Pearson
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Brown
mesh_terms: D000368:Aged; D002448:Cell Adhesion; D016207:Cytokines / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism; D005260:Female; D006801:Humans; D039441:Integrin alpha4 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009504:Neutrophils / Q000378:metabolism*; D010641:Phenotype; D017452:Receptors, IgG / Q000097:blood*; D018805:Sepsis / Q000097:blood*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D017452:Receptors, IgG; D039441:Integrin alpha4