title: Red blood cells stimulate human lung fibroblasts to secrete interleukin-8.
abstract: Following lung injury, red blood cells (RBC) may interact with extracellular matrix (ECM). Fibroblasts, the resident cell in the ECM, have the capacity to produce and secrete a variety of mediators including interleukin-8 (IL-8). In the present study we hypothesized that RBC, or soluble factors released from them, may stimulate IL-8 production by fibroblasts. Fibroblasts were cultured in a three-dimensional collagen gel culture system in the presence or absence of RBC or conditioned medium from RBC (RBC-CM). IL-8 release from fibroblasts was significantly increased when cultured with RBC or RBC-CM and both tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) further stimulated this IL-8 secretion. The enhanced production of IL-8 within fibroblasts was accompanied by increased IL-8 mRNA expression. To evaluate whether RBC-fibroblast interaction may lead to recruitment of neutrophils, a functional migration assay was performed. RBC and RBC-CM, in the presence of IL-1beta and TNF-alpha, increased the transmigration of neutrophils. Our results indicate that RBC, when interacting with ECM, may participate in the recruitment of inflammatory cells by stimulating fibroblasts to secrete IL-8. This might be an important mechanism regulating tissue repair after injury.
authors.affiliation: Department of Medicine, Division of Respiratory Medicine, Karolinska Hospital, Stockholm, Sweden. karin.fredriksson@ks.se
authors.forename: K
authors.initials: K
authors.lastname: Fredriksson
authors.forename: J
authors.initials: J
authors.lastname: Lundahl
authors.forename: L
authors.initials: L
authors.lastname: Palmberg
authors.forename: D J
authors.initials: DJ
authors.lastname: Romberger
authors.forename: X D
authors.initials: XD
authors.lastname: Liu
authors.forename: S I
authors.initials: SI
authors.lastname: Rennard
authors.forename: C M
authors.initials: CM
authors.lastname: Skold
mesh_terms: D002478:Cells, Cultured; D002633:Chemotaxis; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004912:Erythrocytes / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000166:cytology*; D009504:Neutrophils / Q000166:cytology; D019899:Paracrine Communication; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D017077:Culture Media, Conditioned; D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha