The presence of tryptase-positive and bikunin-negative mast cells in psoriatic skin lesions

Abstract

Human mast cells are well known to produce a serine protease, tryptase, which appears to play a pathogenic role in various skin inflammations. It was previously reported that a rat homologue of bikunin may inhibit tryptase activity. Various type of cells (i.e. keratinocytes) are able to produce this protein inhibitor, it still remains unclear if bikunin is present in dermal inflammatory milieu, in which mast cells, through secretion of tryptase, play an inflammatory role. Therefore, the purpose of the present study was to exploit expression and production of bikunin in dermis and dermal constituents. We first compared the dermal mast cells in psoriatic lesions with those in lesional skin of atopic dermatitis or of chronic eczema by use of immunoelectron microscopy and immunohistochemical analyses using antibodies to bikunin and tryptase. Then, we tested what kinds of cytokines may regulate the de novo synthesis of bikunin. To do so, RNA was extracted from a human mastocytic cell line, HMC-1, reverse-transcribed, and semiquantitative RT-PCR was performed using primers specific for bikunin. With immunoelectron microscopy, bikunin was found to localize on the cell membrane, while tryptase was in the secretary granules of the mast cells. In psoriatic lesions, around 70% of dermal mast cells were positive for both tryptase and bikunin, and the remaining was mostly positive for tryptase, but the expression of bikunin was under the detection limit of the experimental setting. This observation was seen in only psoriatic lesions, even in almost cured lesions, while in atopic dermatitis or chronic eczema only mast cells doubly positive for bikunin and tryptase were seen. In HMC-1, bikunin was constitutively expressed at an mRNA level, which was upregulated by stimulation with interleukine-4, but was suppressed by interferon-gamma. Bearing in mind the concept that in psoriasis local cytokine milieu is shifted toward a Th1 pattern (predominant secretion of interferon-gamma), tryptase-positive, bikunin-negative mast cells may be induced.

Serum mast cell tryptase is not a useful marker for disease severity in psoriasis or atopic dermatitis

“…18 The number of mast cells is increased in lesional skin of patients with psoriasis and these mast cells mainly contain tryptase. [19][20][21][22] In a model of early relapsing psoriasis mast cell activation was the first initial event observed in an evolving new psoriasis lesion as demonstrated by conventional histology and electron microscopy. 23 Thus mast cells may trigger the inflammatory reaction in psoriatic lesions by the release of tryptase and possibly promote inflammation already at a very early stage.…”

“…Psoriasis is a chronic inflammatory skin disorder with a genetic susceptibility and a major involvement particularly of the innate immune system 18 . The number of mast cells is increased in lesional skin of patients with psoriasis and these mast cells mainly contain tryptase 19–22 . In a model of early relapsing psoriasis mast cell activation was the first initial event observed in an evolving new psoriasis lesion as demonstrated by conventional histology and electron microscopy 23 .…”

Mast Cells and p53 Expression in Psoriasis Vulgaris

“…9,[18][19][20][21] It is histo pat ho lo gi cally cha rac te ri zed by pa ra ke ra to sis, Turkiye Klinikleri J Med Sci 2011;31 (2) hyper ke ra to sis, re gu lar acant ho sis, elon ga ti on of the epi der mal re te rid ges, elon ga ti on and ede ma of the der mal pa pil la e, and lymphocy tic cell in fil tra tion. 11,[21][22][23] This was al so con fir med in our study. Psori a sis usu ally runs a chro nic co ur se alt ho ugh spon tane o us or tre at ment-in du ced re mis si ons may oc cur.…”

“…1,3,[11][12][13]21 The se in di ca te a po ten ti al ini ti a tor ro le of mast cells in the pat ho ge ne sis of pso ri a sis. 1,13 Mast cell-me di a ted vascu lar al te ra ti on is sug ges ted to play a ro le in the deve lop ment of pso ri a sis.…”

The cholinergic system in guttate psoriasis with special reference to mast cells

“…In addition, there is an increased content of acetylcholine in the psoriatic lesions (3). Degranulated mast cells are characteristic of guttate psoriasis lesions (4,5,6) and can be activated by a great variety of different stimuli, amongst them, acetylcholine (7). We therefore examined the cholinergic system of guttate psoriasis skin with special respect to mast cells.…”