The effect of trauma on neutrophil L-selectin expression and sL-selectin serum levels.
Among identified adhesion molecules, the L-selectin on neutrophils enables the first step of leukocyte adherence to activated endothelial cells. To allow firm adhesion of neutrophils, L-selectin is then split off the cell membrane. It was hypothetized that an increase of the constitutively high serum level of soluble L-selectin may indicate an ongoing pathological neutrophil sequestration to the endothelial cells associated with activation and injury of the cells. To evaluate this hypothesis, sL-selectin serum levels and neutrophil L-selectin expression of healthy volunteers (group A, n = 15), as well as of surgical patients, were investigated. Group B (n = 26) included patients subjected to elective limb surgery (mean operation time, 122 min), and group C (n = 45) comprised trauma patients. sL-selectin serum levels were measured daily over a 14-day period. Neutrophil L-selectin expression was evaluated by FACS analysis using the humanized anti-L-selectin antibody HuDreg 55 over a period of 3 days at minimum in both experimental groups. The binding of sL-selectin to endothelial cells was also examined in vitro. Elective limb surgery resulted in lower pre- and post-operative sL-selectin plasma levels (800-1,000 ng/mL) compared to healthy volunteers (1,100-1,200 ng/mL) with insignificant changes throughout the study period. Trauma patients revealed even lower sL-selectin levels (400-600 ng/mL). When these patients were discriminated by the multiple organ dysfunction (MOD) score of Moore in +MOD (n = 9, ISS = 31.7) and -MOD (n = 36, ISS = 25.0), a significant difference became evident. In +MOD patients sL-selectin levels remained on a low basis of 350 ng/mL, whereas in -MOD patients the initial low sL-selectin level subsequently rose to 800 ng/mL, similar to that of elective surgery patients. FACS analysis revealed a significant drop in neutrophil L-selectin expression 24 h after trauma compared to normal. Also, +MOD and -MOD patients were significantly discriminated by the L-selectin expression at this time. The in vitro studies revealed evidence for binding of sL-selectin to endothelial cells independently on the presence of neutrophils. According to our data, increasing severity of the post-operative/posttraumatic course is associated with decreasing sL-selectin serum levels and also reduced neutrophil L-selectin expression. In view of the in vitro results, this probably indicates competitive enhanced binding of sL-selectin to endothelial cells, thus masking the elevated activation of neutrophils and their ability for endothelial adherence.
Seekamp
A
A
Unfallchirurgische Klinik, Medizinische Hochschule Hannover, FRG.
van Griensven
M
M
Hildebrandt
F
F
Brauer
N
N
Jochum
M
M
Martin
M
M
D000293:Adolescent; D000328:Adult; D002448:Cell Adhesion; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D017558:Elective Surgical Procedures; D004730:Endothelium, Vascular / Q000473:pathology; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D019041:L-Selectin / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology; D009104:Multiple Trauma / Q000097:blood / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000378:metabolism; D012720:Severity of Illness Index; D012995:Solubility; D014947:Wounds and Injuries / Q000097:blood / Q000235:genetics / Q000276:immunology*
D011994:Recombinant Proteins; D019041:L-Selectin