Granulocyte extravasation and recruitment to sites of interstitial inflammation in patients with renal failure.
BACKGROUND
We have shown that leukocytes collected from sites of interstitial inflammation in patients on hemodialysis have a disturbed expression of CD11b compared to cells from healthy subjects. The aim of the present study was to study adhesion molecule expression on granulocytes in the peripheral circulation and at sites of interstitial inflammation in patients with renal failure.


METHODS
Two skin blisters were raised in 10 patients and 19 healthy subjects and interstitial exudates collected (0 h). Skin chambers were applied and exposed to buffer or serum for 10 h in order to induce an intermediate and an intense interstitial inflammation. Cells and blister fluid were collected for determination of leukocyte count, CD11b/CD62L expression, interleukin-8 (IL-8) concentration in the interstitium and blister activity in terms of CD11b up-regulation.


RESULTS
At the sites of intermediate and intense inflammation, granulocytes from patients with renal failure showed significantly higher expression of CD62L (p < 0.01 and p < 0.001, respectively) and significantly lower expression of CD11b (p < 0.0001 and p < 0.0001, respectively) compared to corresponding cells from healthy subjects. The interstitial concentration of IL-8 was significantly lower at the sites of intermediate (p < 0.005) and intense inflammation (p < 0.05) in patients with renal failure compared to in healthy subjects. In order to explore whether the decreased CD11b expression observed in patients is due to the interstitial milieu, blister exudates from patients and healthy subjects were incubated with leukocytes from healthy blood donors. Blister exudates from patients had a similar capacity to mobilize CD11b on granulocytes in vitro compared with blister exudates from healthy subjects. There was no consistent correlation between the expression of adhesion molecules on granulocytes in the interstitium and the concentration of IL-8 or the total interstitial concentration of chemotactic mediators.


CONCLUSIONS
Constitutive cellular determinants are probably involved in the disturbed expression of adhesion molecules on granulocytes at sites of interstitial inflammation in patients with renal failure.
Dadfar
Elham
E
Department of Clinical Immunology, Karolinska Hospital, Stockholm, Sweden.
Lundahl
Joachim
J
Jacobson
Stefan H
SH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001768:Blister / Q000473:pathology; D039481:CD11b Antigen / Q000096:biosynthesis; D002465:Cell Movement; D002478:Cells, Cultured; D005260:Female; D006098:Granulocytes / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000276:immunology*; D051437:Renal Insufficiency / Q000097:blood*
D039481:CD11b Antigen; D016209:Interleukin-8