Recruitment of neutrophils in the local endotoxin response: association with de novo endothelial expression of endothelial leukocyte adhesion molecule-1.
Endothelium is central to the cellular infiltration that develops during inflammation, and a prominent feature of its involvement is the expression of adhesion molecules for circulating leukocytes. In the present study, we assessed the kinetics of endothelial adhesion molecule expression during the cutaneous endotoxin response in baboons. Immunostained cryostat sections and hematoxylin and eosin-stained paraffin sections of skin biopsies were examined using set scoring systems to provide semiquantitative data on the changes in endothelial phenotype and induced polymorphonuclear leucocyte (PMN) accumulation. Endothelium in control skin did not express endothelial leukocyte adhesion molecule (ELAM)-1 but did show a relatively weak expression of intercellular adhesion molecule (ICAM)-1. By 2 hours after injection of endotoxin (500 mcg of Escherichia coli-derived lipopolysaccharide), a marked expression of ELAM-1 developed that was associated with concurrent extensive adhesion and extravasation of PMN. The ELAM-1 expression subsequently decreased and was virtually absent by 9 hours. Mean scores for endothelial expression of ICAM-1 changed comparatively little over this time course, and mononuclear cell accumulation was minimal. The response to endotoxin differs from that to tumor necrosis factor injection; the latter causes sustained ELAM-1 expression, and delayed but pronounced increases in ICAM-1, with accompanying mononuclear cell extravasation. Thus, local endotoxin administration provides a model of acute inflammation in which PMN accumulation is associated with striking endothelial expression of ELAM-1. In this model, appreciable elevations in ICAM-1 expression are unnecessary for PMN infiltration.
Munro
J M
JM
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
Pober
J S
JS
Cotran
R S
RS
D000818:Animals; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000096:biosynthesis*; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004731:Endotoxins / Q000633:toxicity; D005260:Female; D007700:Kinetics; D009504:Neutrophils / Q000473:pathology / Q000502:physiology*; D010215:Papio; D012772:Shock, Septic / Q000473:pathology* / Q000503:physiopathology; D012867:Skin / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D004731:Endotoxins