E-selectin-dependent neutrophil adhesion to Rickettsia rickettsii- infected endothelial cells

Abstract

Increased neutrophil or HL60 cell adhesion to Rickettsia rickettsii- infected endothelial cells (ECs) was observed at 6 to 8 hours after the initiation of infection, diminishing by 24 hours. Similar increases were observed using formaldehyde-fixed neutrophils. Cellular association and likely the intracellular presence of rickettsiae was required for enhanced neutrophil adhesion, because culture medium conditioned by infected cells or rickettsiae rendered noninfective by pretreatment with tetracycline were ineffective at inducing neutrophil adhesion. Increases in neutrophil adhesion caused by infection were blocked by pretreatment of ECs with cycloheximide, suggesting the involvement of new protein synthesis in the cells' response. Flow cytometric analysis of infected cells showed increases in cell surface expression of E-selectin compared with uninfected control cells. Furthermore, incubation of 6- to 8-hour infected cells with a blocking monoclonal antibody against E-selectin (BB11) inhibited neutrophil adhesion an average of 61%. These results suggest the involvement of E- selectin in neutrophil adhesion to infected ECs occurring early in the course of the infection process. EC-initiated recruitment of neutrophil adhesion during rickettsiae infection could contribute to the pathologic changes associated with Rocky Mountain Spotted Fever.

Effect of Blocking the Cxcl9/10-Cxcr3 Chemokine System in the Outcome of Endothelial-Target Rickettsial Infections

“…As a consequence of rickettsial infection, these cells express an inflammatory phenotype which includes cytokines such as IL-1␣, IL-6, and IL-8, 27,28 and adhesion molecules including ICAM-1, VCAM-1, 29 and endothelialleukocyte adhesion molecule 1. 30 Our results led us to hypothesize that antigenic presentation by endothelial cells in the context of increased expression of inflammatory adhesion molecules might be sufficient to trigger the effector mechanisms of anti-rickettsial T cells and in this way may bypass the requirement for chemokines. In support of this hypothesis, the present study demonstrated that the expression of ICAM-1 and VCAM-1, previously reported using in vitro models, as a consequence of a rickettsial infection, 29 also occurs in vivo in an animal model of spotted fever group rickettsiosis ( Figure 5).…”

The Blood-Brain Barrier and Its Role in Inflammation

“…The gene products that are increasingly expressed are TF, the proinflammatory cytokine IL-1␣, and the adhesion molecule E-selectin. [187][188][189][190] These findings explain some of the clinical and pathological findings found in RMSF.…”

Tropism and Pathogenicity of Rickettsiae

“…However, EC are not only injured by infection, but also initiate cellular responses such as endothelial activation. Specifically, the infection of EC with R. rickettsii or R. conorii induces surface platelet adhesion (Silverman, 1986 ); the release of von Willebrand factor from Weibel–Palade bodies (Sporn et al, 1991 ; Teysseire et al, 1992 ); and increased expression of tissue factor (Teysseire et al, 1992 ; Sporn et al, 1994 ), E-selectin (Sporn et al, 1993 ), IL-1α (Kaplanski et al, 1995 ; Sporn and Marder, 1996 ), cell-adhesion molecules (Dignat-George et al, 1997 ), and plasminogen activator inhibitor-1 (Drancourt et al, 1990 ; Shi et al, 2000 ). The infection of EC with the TGR R. prowazekii resulted in enhanced prostaglandin secretion (Walker et al, 1990 ).…”