The leukocyte adhesion molecule CD llb is very important when granulocytes and monocytes leave the blood stream. This adhesion molecule is stored preformed intracellularly, and can upon stimulation of the cells by, for example, complement split products, be mobilized to the cell surface. CD14 a differentiation antigen and an endotoxin receptor, is found mainly on monocytes, that can be upregulated during stimulation. Upon monocyte CD 14 interactions with endotoxin, pro-inflammatory cytokines like TNF-a. can be produced.
The aim of this work was to detect signs of activation of the complement system, leukocyte activation with receptor mobilization and alterations in the plasma levels of soluble selectins, as wen as evidence of cytokineproduction, in model situations of systemic inflammatory responses. For this patients were monitored during the first week after a severe bum damage. We found evidence of complement activation, increased levels of soluble E-selectin as an indication of systemic inflammation, and cytokine production. During surgical revision of burn wounds we detected increased expression of granulocyte CD llb in response to plasma endotoxin liberation, and increased plasma levels of iL-6.
In another model situation we studied patients on heart-lung machines undergoing open heart surgery, using heparin-coated or uncoated cardiopulmonary systems. Using uncoated systems, a profound early complement activation was found, leading to rapid mobilization of granulocyte CD llb to the cell surface. We also detected a loss of circulating monocytes during bypass. Neither of these effects were detected when heparin-coated systems were used. Increased monocyte L-selectin expression was found in both groups during bypass, interpreted as a result of redistribution of cells. Plasma levels of soluble L-selectin decreased during early bypass in both groups, probably as a result of dilution of the blood with solutions of the circuit.
In the monocyte population, we discovered mobilization of CD 14 during bypass using uncoated systems, but not when coated systems were used. We also found increased plasma endotoxin levels after 5 min of bypass,irrespective of which system was used. Despite the presence of endotoxin, together with increased CD14 expression in the uncoated group, we did not find significant differences between the groups in terms of plasma levels ofTNF-o or IL-6.
To conclude, we found rapid alterations in the granulocyte CDllb and monocyte CD14 expression upon stimulation with endotoxin and/or complement products. Monitoring rapid alterations in the activity state ofimportant effector cells in the inflammatory system is thus possible, by studying alterations in their receptor expression.
Linköping: Linköpings universitet , 1996. , 52 p.
Papers, included in the Ph.D. thesis, are not registered and included in the posts from 1999 and backwards.