Activated macrophages are essential in a murine model for T cell-mediated chronic psoriasiform skin inflammation.
The CD18 hypomorphic (CD18hypo) PL/J mouse model clinically resembling human psoriasis is characterized by reduced expression of the common chain of beta2 integrins (CD11/CD18) to only 2-16% of WT levels. Previously we found that this chronic psoriasiform skin inflammation also depends on the presence of CD4+ T cells. Herein we investigated the role of macrophages in this CD18hypo mouse model. Activated macrophages were significantly increased in lesional skin as well as in inflamed skin draining lymph nodes (DLNs) of affected CD18hypo mice and were identified as being an important source of TNF-alpha in vivo. Both depletion of macrophages and neutralization of TNF-alpha resulted in a significant alleviation of psoriasiform skin inflammation. As monocyte chemotactic protein 1 was enhanced in lesional skin of affected CD18hypo mice, we intradermally injected recombinant murine monocyte chemotactic protein-1 (rJE/MCP-1) alone or in combination with rTNF-alpha into the skin of healthy CD18hypo mice. Only simultaneous injection of rJE/MCP-1 and rTNF-alpha, but neither substance alone, resulted in the induction of psoriasiform skin inflammation around the injection sites with recruitment and activation of macrophages. Collectively, our data suggest that maintenance of psoriasiform skin inflammation critically depends on efficient recruitment and activation of macrophages with sufficient release of TNF-alpha.
Wang
Honglin
H
Department of Dermatology and Allergic Diseases, University of Ulm, Ulm, Germany.
Peters
Thorsten
T
Kess
Daniel
D
Sindrilaru
Anca
A
Oreshkova
Tsvetelina
T
Van Rooijen
Nico
N
Stratis
Athanasios
A
Renkl
Andreas C
AC
Sunderkötter
Cord
C
Wlaschek
Meinhard
M
Haase
Ingo
I
Scharffetter-Kochanek
Karin
K
D000818:Animals; D018845:CD11 Antigens / Q000276:immunology; D018821:CD18 Antigens / Q000235:genetics / Q000276:immunology; D018932:Chemokine CCL2 / Q000235:genetics / Q000494:pharmacology; D004195:Disease Models, Animal; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D008262:Macrophage Activation / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D010641:Phenotype; D011565:Psoriasis / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*
D018845:CD11 Antigens; D018821:CD18 Antigens; D018932:Chemokine CCL2; D012333:RNA, Messenger; D011994:Recombinant Proteins