title: Hemodialysis-activated granulocytes at the site of interstitial inflammation.
abstract: It is not known to what extent intravascular phenotypic alterations in adhesion molecule expression induced by hemodialysis influence the recruitment of granulocytes and their ability to up-regulate CD11b at the local site of inflammation in the interstitium. We used a skin suction chamber technique to address this issue. Two skin blisters were raised on the forearm of eight hemodialysis patients and eight healthy subjects, and blister exudate was collected (time 0). The two blisters were stimulated with buffer (intermediate inflammation) or autologous serum (intense inflammation). Then the patients underwent cuprophane hemodialysis for 4 hours. Ten hours after start of dialysis, the exudate was aspirated from each chamber. Granulocyte count and surface expression of CD11b and CD62L were analyzed in samples from peripheral blood and blister exudate by flow cytometry. Granulocytes from healthy blood donors were incubated in blister fluid from patients and healthy subjects to determine the local chemotactic activity in terms of CD11b up-regulation. The expression of CD11b increased fourfold and CD62L decreased simultaneously in patients and healthy subjects when cells transmigrated to the unstimulated blister at time 0. At the site of intermediate inflammation, granulocytes from patients had a significantly lower capacity to mobilize CD11b compared with cells from healthy subjects (P < 0.001). At the site of intense interstitial inflammation, granulocytes from patients had the capacity to mobilize the receptor and reached values close to those obtained in healthy subjects (P = 0.079). The blister exudate from patients had a similar (at time 0 and intermediate inflammation) or higher (intense inflammation; P < 0.05) capacity to up-regulate CD11b on granulocytes in vitro compared with blister exudate from healthy subjects. Granulocytes from hemodialysis patients seem to require a more intense chemotactic stimulus to up-regulate CD11b at the local site of inflammation in the interstitium compared with corresponding cells from healthy subjects despite the fact that cells transmigrate in a milieu that contains chemotactic factors with an equal or higher capacity to up-regulate CD11b. Granulocytes in hemodialysis patients seem to be more refractory to inflammatory stimuli in the interstitium.
authors.affiliation: Department of Nephrology, and Division of Clinical Immunology, Karolinska Hospital and Karolinska Institute, Stockholm, Sweden. stefan.jacobson@ks.se
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Jacobson
authors.forename: Pia
authors.initials: P
authors.lastname: Thylén
authors.forename: Eva
authors.initials: E
authors.lastname: Fernvik
authors.forename: Gunilla
authors.initials: G
authors.lastname: Halldén
authors.forename: Reidar
authors.initials: R
authors.lastname: Grönneberg
authors.forename: Joachim
authors.initials: J
authors.lastname: Lundahl
mesh_terms: D000328:Adult; D000368:Aged; D001768:Blister / Q000473:pathology*; D018821:CD18 Antigens; D002465:Cell Movement; D006098:Granulocytes / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D019041:L-Selectin / Q000096:biosynthesis; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D008875:Middle Aged; D006435:Renal Dialysis; D012871:Skin Diseases / Q000473:pathology
chemical_list: D018821:CD18 Antigens; D016177:Macrophage-1 Antigen; D019041:L-Selectin