The inter-relation between inflammation and epidermal proliferation in normal skin following epicutaneous application of leukotriene-B4-an immunohistochemical study

Abstract

Topical application of leukotriene-B4 (LTB4) on normal skin has been used as an in-vivo model to investigate cutaneous inflammation and epidermal proliferation, which are important phenomena in the pathogenesis of psoriasis. The aim of the present investigation is to further elucidate the interrelation between inflammation and epidermal proliferation, using specific monoclonal antibodies as markers for the different cell types involved. Aliquots of LTB4 were applied on the upperarms of eight healthy volunteers. After LTB4-application, biopsies were taken at consecutive time intervals. On frozen sections, epidermal proliferation was assessed by Ks8.12-(keratin 16) and Ki-67-binding (cycling cells), inflammation was characterized using anti-elastase (PMN), T11 (T-lymphocytes), pan-B (B-lymphocytes), WT 14 (CD14-positive cells) and OKT 6 (Langerhans cells). New observations were that the density of CD14-positive cells was increased even at 8 h and decreased slightly at 72 h. A striking rearrangement of Langerhans cells was seen in close vicinity to intra-epidermal accumulations of PMN. Remarkably an increased density of these cells in the dermis at 72 h was seen and a decrease in the epidermis. In line with previous studies, the accumulation of PMN reached a maximum 24 h after LTB4-challenge. The identity of the mononuclear infiltrate cells which have been reported 48-72 h after LTB4 proved to be T-lymphocytes. No B-lymphocytes were observed. Ki-67-positive nuclei were maximally increased 72 h after LTB4-application, which implies that recruitment of cycling cells is of relevance for the LTB4-induced proliferation in vivo. The hyperproliferation-related keratin 16 was expressed inconsistently in the suprabasal compartment.(ABSTRACT TRUNCATED AT 250 WORDS)

Cutaneous Application of Leukotriene B₄ as an in vivo Model of Psoriasis-Like Skin Inflammation: An Immunohistological Study

“…Furthermore, the changes in proliferation and differentiation markers found after challenging the skin resemble the findings of previous studies [8,9,19], indicating that this model is highly reproducible and that the execution of the LTB 4 application was done accurately.…”

“…During the past decades, the inflammatory response to epicutaneous application of leukotriene B 4 (LTB 4 ) has been studied extensively and can be regarded as an established model to mimic psoriasis-like inflammation of the skin [8,9,10,11,12]. It is known that in psoriatic lesions high levels of LTB 4 are present [13,14] which are produced by activated innate immune cells [15,16].…”

Leukotriene B4 Driven Neutrophil Recruitment to the Skin Is Essential for Allergic Skin Inflammation

“…Studies in Lta4h −/− and Ltb4r1 −/− mice demonstrated that LTB 4 and BLT1 are both important for neutrophil accumulation into tape-stripped mouse skin. The role of LTB 4 in neutrophil recruitment to the skin is supported by the observation that epicutaneous application of LTB 4 in normal healthy volunteers results in local neutrophil infiltration (de Jong et al, 1992). LTB 4 induces itch-associated scratching response in mice (Kim et al, 2007).…”

The leukotriene B4 lipid chemoattractant receptor BLT1 defines antigen-primed T cells in humans

“…Prior to the identification of BLT1, it was shown that LTB 4 bound a small proportion of human peripheral blood T cells 11,12 and could induce their chemotaxis both in vitro and in vivo after topical application of LTB 4 . 11,13 Studies have noted very low-level expression of BLT1 in human peripheral blood T cells as measured by RNA levels or cell surface protein expression. 14,15 The phenotype and function of human BLT1 ϩ T cells and the functional significance of the LTB 4 -BLT1 lipid chemoattractant pathway in human adaptive immune cell trafficking, therefore, still remain to be defined.…”