Myeloid cell populations and fibrogenic parameters in bleomycin- and HOCl-induced fibrosis.

Experimental dermatology

PubMedID: 27307019

Raker VK, Yong Ook K, Haub J, Lorenz N, Schmidt T, Stegemann A, Böhm M, Schuppan D, Steinbrink K. Myeloid cell populations and fibrogenic parameters in bleomycin- and HOCl-induced fibrosis. Exp Dermatol. 2016;.
Mouse models resembling systemic sclerosis can be chemically induced by application of bleomycin or hypochloric acid (HOCl). To date little is known about inflammatory cells and their potential role in scleroderma (Scl)-related fibrosis. Therefore, we compared both Scl-models to define the early immune cell subsets in relation to fibrosis-related parameters. Both agents induced a significant increase in dermal thickness and collagen deposition after four weeks, as hallmarks of Scl. However, clinical skin thickness, densely packed, sirius red stained collagen bundles and collagen crosslinks were more pronounced in HOCl-induced Scl. In parallel, there was a significant upregulation of procollagen a1(I), a-SMA and TGF-ß transcripts in HOCl animals, whereas IL-1ß and MMP-13 mRNA levels were significantly increased in bleomycin-treated mice. Flow-cytometric analysis of the Scl skin demonstrated an early cellular infiltrate containing mainly CD19(+) B cells, CD4(+) T cells, CD11c(+) DC and CD11b(+) myeloid cells, the latter ones being significantly more prominent after HOCl injection. Sub-analysis revealed that Scl mice exhibited a significant increase of inflammatory myeloid CD11b(+) Ly6C(low-high) CD64(low-high) cells (HOCl>bleomycin). Especially in the HOCl model, activated dermal macrophages (CCR2(low) MHCII(high) ) and monocyte-derived DC (CCR2(high) MHCII(high) ) predominated over less activated CD11b(+) myeloid cells. In conclusion, the two models differ in certain aspects of the murine and human scleroderma but in the HOCl-model, myeloid CD11b(+) MHCII(high) cells correlate with some fibrosis related parameters. Therefore, analysis of both models is suggested to cover a comprehensive profile of Scl symptoms but with focus on the HOCl model when the role of early myeloid immune cells will be evaluated. This article is protected by copyright. All rights reserved.