title: Psoriatic keratinocytes prime neutrophils for an overproduction of superoxide anions.
abstract: Psoriatic plaques result from an abnormal proliferation of keratinocytes associated with the local presence of T lymphocytes and neutrophils. The exact role of neutrophils in psoriatic lesions remains unclear. The present investigation was aimed at deciphering the capacity of psoriatic keratinocytes to alter in vitro functions of neutrophils. Blood neutrophils from healthy donors were incubated with psoriatic (PK) or healthy keratinocytes (HK) with and without IL-2-activated healthy T lymphocytes. The study was focussed on neutrophil capacity of adherence, viability and superoxide anion production. PK or HK with or without T lymphocytes similarly augmented neutrophil viability after 48 h of co-incubation. PK or HK did not directly activate the superoxide production by neutrophils. However, they both primed neutrophils for an increased fMLF-induced production of superoxide, an effect enhanced by the presence of T lymphocytes. PK were 1.5-fold more efficient than HK to augment this superoxide production. PK cultured with T lymphocytes induced the adhesion of neutrophils 4.7 times more efficiently than HK. The adherence of neutrophils was mediated through ICAM-1, LFA-1 and Mac-1, independently of bioactive lipids. The effects of PK and HK on neutrophil viability and priming were independent of direct cellular contact. In conclusion, keratinocytes can impact neutrophils by increasing their lifespan, and by priming them to overproduce superoxide. PK are more efficient than HK in priming neutrophils, an effect enhanced by T lymphocytes. These results indicate that neutrophils could contribute to psoriasis pathogenesis partly through their pathological interactions with PK.
authors: Laboratoire d'Organogénèse Expérimentale (LOEX), Centre de Recherche FRSQ du CHU de Québec, Québec, Canada.
authors: Simon
authors: S
authors: Guérard
authors: Isabelle
authors: I
authors: Allaeys
authors: Guillaume
authors: G
authors: Martin
authors: Roxane
authors: R
authors: Pouliot
authors: Patrice E
authors: PE
authors: Poubelle
mesh_terms: D002448:Cell Adhesion / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D007376:Interleukin-2; D015603:Keratinocytes / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D018384:Oxidative Stress / Q000276:immunology; D011565:Psoriasis / Q000276:immunology* / Q000473:pathology; D013481:Superoxides / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: C573420:ICAM1 protein, human; C508594:IL2 protein, human; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D013481:Superoxides; D018799:Intercellular Adhesion Molecule-1