title: In-vivo extravasation induces the expression of interleukin 1 receptor type 1 in human neutrophils.
abstract: In order to address neutrophil activation during inflammation we assessed the expression of interleukin 1 receptor type 1 (IL-1R1) following in-vivo extravasation. Extravasated neutrophils were collected from 11 healthy study subjects by a skin chamber technique and compared to neutrophils in peripheral blood. Expression of IL-1R1 was assessed by microarray, quantitative polymerase chain reaction (qPCR), Western blot, flow cytometry, enzyme linked immunosorbent assay (ELISA) and immunoelectron microscopy (iEM). IL-1R1 was induced following extravasation, demonstrated by both gene array and qPCR. Western blot demonstrated an increased expression of IL-1R1 in extravasated leucocytes. This was confirmed further in neutrophils by flow cytometry and iEM that also demonstrated an increased intracellular pool of IL-1R1 that could be mobilized by N-formyl-methionine-leucine-phenylalanine (fMLP). Stimulation of peripheral neutrophils with IL-1 resulted in transcription of NFκB and a number of downstream chemokines and the corresponding chemokines were also induced following in-vivo extravasation. The present results demonstrate that IL-1R1 is induced following extravasation and exists on the neutrophil surface, as well as in a mobile intracellular pool. Furthermore, neutrophils express functional IL-1R1 as demonstrated by the induction of chemokines following IL-1 stimulation. The results indicate a potential role for IL-1 in the activation of neutrophils at inflammatory sites.
authors.affiliation: Institution of Medicine, Departmentof Clinical Immunology and Allergy,Karolinska University Hospital, Solna, Stockholm, Sweden. josefin.paulsson@ki.se
authors.forename: J M
authors.initials: JM
authors.lastname: Paulsson
authors.forename: A
authors.initials: A
authors.lastname: Moshfegh
authors.forename: E
authors.initials: E
authors.lastname: Dadfar
authors.forename: C
authors.initials: C
authors.lastname: Held
authors.forename: S H
authors.initials: SH
authors.lastname: Jacobson
authors.forename: J
authors.initials: J
authors.lastname: Lundahl
mesh_terms: D000368:Aged; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D053582:Interleukin-1alpha / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D053573:Receptors, Interleukin-1 Type I / Q000096:biosynthesis* / Q000097:blood; D015375:Receptors, Interleukin-2 / Q000097:blood; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D018925:Chemokines; D007375:Interleukin-1; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D016328:NF-kappa B; D053573:Receptors, Interleukin-1 Type I; D015375:Receptors, Interleukin-2; D009240:N-Formylmethionine Leucyl-Phenylalanine