Localization of IL-8 and Complement Components in Lesional Skin of Psoriasis vulgaris and Pustulosis palmaris et plantaris

Abstract

Background: Munro’s microabscesses are a characteristic histopathologic feature of psoriasis vulgaris; however, the pathomechanisms underlying the migration of transepidermal leukocytes (PMNs) have not been fully elucidated yet. Objective and Methods: Since the lesional scale extracts contain potent chemoattractants, such as IL-8 and C5a fragments, we studied their location in the lesions of psoriasis vulgaris and PPP with immunohistochemical techniques. Results: Localization of IL-8 was not detected in the subcorneal keratinocytes but was demonstrated only in the basal keratinocytes together with migrating PMNs. In contrast, the presence of a complement fragment, C3b, was observed on the cell membranes of subcorneal keratinocytes, suggesting that these were the sites of complement activation. Conclusion: Such distinct localization of IL-8 and complement components suggests that the intraepidermal migration of PMNs takes place first according to the concentration gradient of IL-8, and thereafter they are guided by complement components to the final destination, the subcorneal portion of the lesional skin.

Concomitant activation of P2Y2 and P2Y6 receptors on monocytes is required for TLR1/2‐induced neutrophil migration by regulating IL‐8 secretion

“…As IL-8 secreted by a variety of inflammatory cells including monocytes has been implicated in a number of inflammatory/infectious diseases, such as rheumatoid arthritis [33], inflammatory bowel disease [34], psoriasis [35,36], palmoplantar pustulosis [37,38], asthma and chronic obstructive pulmonary disease [39], targeting P2Y 2 and/or P2Y 6 receptors may reveal as novel therapeutic approaches to fight these diseases. These data are also in agreement with a new concept proposing that extracellular nucleotides serve as endogenous danger-signaling molecules called alarmins that are (10 ng/mL) for 5 h in the presence or absence of semi-purified apyrase (2 U/mL) and/or P2 receptor antagonists (100 mM RB2, suramin, PPADS, or 10 mM MRS2578, respectively).…”

Induction of C3 and CCL2 by C3a in Keratinocytes: A Novel Autocrine Amplification Loop of Inflammatory Skin Reactions

“…In KCs, induction of C3 by C3a clearly suggests the amplification of C3a mediated effects in an autocrine fashion. Local expression of C3, pivotal to complement activation pathways, was described in a range of inflammatory skin disorders such as psoriasis and allergic contact dermatitis (30). Inhibition of the C3 synthesis in KCs by psoralen and UVA light therapy and UVA has been suggested as one of the mechanism to suppress the effector phase of the immune response for the many skin diseases such as psoriasis (53).…”

“…C3 fragments are also found intralesionally in inflammatory diseases such as psoriasis (27), eczema (28), and asthma (19,29). Recently, C3b deposition was detected in the stratum corneum of the lesions of psoriasis vulgaris, and a cytoplasmic distribution of C3b as well as C3a was observed in the subcorneal to spinous KCs of allergic contact dermatitis, AD, and psoriatic lesional KCs (30). In the skin, C3 can be activated by mechanical injury and UV radiation injury (31).…”

IL-8 as Antibody Therapeutic Target in Inflammatory Diseases: Reduction of Clinical Activity in Palmoplantar Pustulosis

“…Aberrant IL-8 production can lead to chronic inflammatory conditions, as suggested for inflammatory diseases such as rheumatoid arthritis (13)(14)(15), inflammatory bowel disease (16), psoriasis (17,18), and palmoplantar pustulosis (PPP) 4 (19,20). Accumulation of activated neutrophils in lesional areas and elevated IL-8 production is observed in all these diseases.…”