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Published on: January 17, 2012
Decreased extracellular release of granule enzymes from in vitro-stimulated polymorphonuclear leukocytes in guttate
Abstract:
In vitro degranulation of polymorphonuclear leukocytes, which were stimulated either with synthetic chemotactic peptide (N-formyl-methionyl-leucyl-phenylalanine, FMLP) or with C3b-opsonized zymosan as a promotor of phagocytosis, was studied in 66 patients with psoriasis, 18 lesion-free psoriatics, 18 healthy subjects, and 14 other dermatological disorder controls. Stimulated release of lysozyme (from specific granules and azurophil granules) and beta-glucuronidase (from azurophil granules) in the presence of both FMLP and serum-activated zymosan was markedly reduced in patients with actively spreading guttate psoriatic lesions, in whom relapse of lesions lasted for less than 1 month and papules involved about 13-25% of skin surface. In contrast, stimulated degranulation was within normal range in active plaque psoriasis, stationary plaque psoriasis, symptomless psoriatics, and patients with disseminated eczema. Spontaneous release of lysozyme and beta-glucuronidase (background) was found to be not different in all groups studied; however, patients with active guttate psoriasis had significantly lower total lysozyme activity than those with active and stationary plaque psoriasis as well as psoriatics in the remission. These data are in favor of in vivo activation of neutrophils in active guttate psoriasis by some factors related to the early relapse of the lesions. This results in a possible combination of the following phenomena: (1) in vivo partial degranulation of neutrophils; (2) induction of "unresponsiveness state" of these cells to subsequent in vitro stimulation; and/or (3) migration of highly responsive neutrophils to skin lesions, which leaves in the circulation the subpopulation less reactive to chemotactic and phagocytic stimuli.
Insights
Neutrophil degranulation, essential for fighting infection, is impaired in active guttate psoriasis. This suggests neutrophils may be pre-activated in vivo, leading to reduced responsiveness in patients with this specific psoriasis subtype.
Area of Science:
- Immunology
- Dermatology
- Cell Biology
Background:
- Polymorphonuclear leukocytes (neutrophils) play a crucial role in immune responses.
- Neutrophil degranulation is a key process involving the release of antimicrobial substances.
- Dysregulation of neutrophil function is implicated in various inflammatory skin conditions like psoriasis.
Purpose of the Study:
- To investigate in vitro neutrophil degranulation in patients with different forms of psoriasis.
- To compare neutrophil function in active guttate psoriasis versus other psoriatic subtypes and controls.
- To explore potential mechanisms underlying altered neutrophil behavior in guttate psoriasis.
Main Methods:
- Studied in vitro degranulation of polymorphonuclear leukocytes (neutrophils).
- Neutrophils were stimulated using N-formyl-methionyl-leucyl-phenylalanine (FMLP) and C3b-opsonized zymosan.
- Measured the release of lysozyme and beta-glucuronidase in 66 psoriasis patients, 18 lesion-free psoriatics, 18 healthy subjects, and 14 controls.
Main Results:
- Markedly reduced stimulated degranulation of neutrophils observed in active guttate psoriasis patients with recent lesion relapse.
- Neutrophil degranulation was normal in active plaque psoriasis, stationary plaque psoriasis, symptomless psoriatics, and eczema patients.
- Active guttate psoriasis patients showed significantly lower total lysozyme activity compared to other psoriatic groups.
Conclusions:
- Suggests in vivo activation and partial degranulation of neutrophils in active guttate psoriasis.
- Hypothesizes an 'unresponsiveness state' or migration of reactive neutrophils to skin lesions.
- Indicates a specific neutrophil dysfunction associated with active guttate psoriasis and early relapse.
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