Demonstration of Rickettsia conorii-induced endothelial injury in vivo by measuring circulating endothelial cells, thrombomodulin, and von Willebrand factor in patients with Mediterranean spotted fever [see comments]

Abstract

The endothelial cell (EC) is the primary target for Rickettsia conorii (RC) in Mediterranean spotted fever (MSF). Clinical manifestations such as thrombosis and vasculitis are mediated by pathologic changes localized in blood vessels. To study the in vivo endothelial injury induced by RC, markers of endothelial damage, including circulating EC (CEC), plasmatic thrombomodulin (TM), and von Willebrand factor (vWF), were investigated in 12 patients with MSF. CEC were counted in whole blood by a new immunomagnetic separation assay using a specific anti-EC antibody, S-Endo 1. Plasmatic TM and vWF antigens were measured by enzyme-linked immunosorbent assay. High levels of CEC and cell fragments were found in patients with a severe or malignant form of MSF. Sequential studies of CEC showed a decrease from 162 +/- 454 cells/mL before treatment to 6 +/- 7 cells/mL during treatment and recovery. Mean plasma TM and vWF levels that were also elevated before therapy (TM, 106 +/- 27 ng/mL; vWF, 420% +/- 164%) decreased progressively (TM, 55 +/- 43 ng/mL; vWF, 148% +/- 26%) during treatment. The measurement of cellular and molecular markers of vascular damage such as CEC, plasmatic TM, and vWF contributes to the definition of the Rickettsia-induced endothelial injury in vivo.

S‐Endo 1, a pan‐endothelial monoclonal antibody recognizing a novel human endothelial antigen

“…This result together with the high and ubiquitous endothelial constitutive expression of the molecule, makes S-Endo 1 a good pan-endothelial marker to isolate endothelial cells from a heterogenous cell population of the hematopoietic lineage. This major property was the basis of S-Endo 1 selection to develop a specific and sensitive method allowing the detection of circulating endothelial cells in vascular disdrders (12,13). More recently, Schweitzer et al have prepared highly purified preparations of human bone marrow endothelium using S-Endo 1 (19).…”

Isolation and enumeration of circulating endothelial cells by immunomagnetic isolation: proposal of a definition and a consensus protocol

“…We reviewed our experience published previously [3,4,[12][13][14][15][16][17][18][19][20][21] and included the data presented here. Based on these data and our own experience, we compiled a list of problems with the isolation and enumeration of CECs and provide recommendations.…”

Circulating endothelial cells in vascular disorders: new insights into an old concept

“…In contrast, elevated values of CEC, ranging from 18 to 1600 cells per millilitre, were detected in patients with malignant or severe forms of the disease who developed thrombotic complications and sometimes required anticoagulant treatment. Thus, the highest values of CEC associated with the malignant forms may be predictive of this potentially lethal form of the disease (10). In immunocompromised patients with disseminated CMV infections, CEC counts >10 per millilitre were associated with high levels of CMV viremia and antigenemia, as well as with an overt clinical syndrome in transplanted patients, and to an untreated long-lasting organ localization in AIDS patients (12).…”

“…The rapid disappearance of CEC from blood within a few days of treatment by ganciclovir and foscarnet in CMVinfected patients suggests that timely initiation of speci®c antiviral treatment might resolve organ involvement (12). In rickettsial infection, the mean CEC level decreased during the ®rst nine days of antibiotic treatment concommitantly with clinical improvement (10). In TTP patients, plasma exchange in combination with vincristine results in a lower CEC level and higher platelet count (13).…”