In‐vivo extravasation induces the expression of interleukin 1 receptor type 1 in human neutrophils

Summary 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 NF κ B 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.