Investigation of inflammatory mechanisms induced by mechlorethamine in mouse ear.
- 1Department of Pharmaceutical Sciences, St. John's University, Queens, NY 11439, USA.
- 2Department of Pharmaceutical Sciences, Ferris State University, Big Rapids, MI 49307, USA.
- 3Center for Advanced Biotechnology and Medicine, Piscataway, NJ 08854, USA.
Abstract
Mechlorethamine (HN2) is toxic to the skin and causes inflammation accompanied by disruption of the dermal-epidermal junction (DEJ), commonly known as vesication. HN2 is a sulfur mustard mimic used in research settings to investigate the pharmaco-toxic effects of vesicants. Effective medical countermeasures for vesicant-induced injury remain limited, underscoring the need to identify novel targets for reducing vesication. The present study used HN2 dissolved in dimethyl sulfoxide (DMSO) to induce mouse ear edema and investigate the contribution of the complement system (CS) to skin responses 24 h after exposure to HN2, with DMSO serving as the vehicle control. Tissues were homogenized and processed for proteomic analysis to examine the protein milieu in skin actively responding to HN2-mediated cutaneous injury. Comparative analysis identified 695 proteins that were differentially expressed between the vehicle- and HN2-treated groups (p < 0.05, fold change ≥1). Of these, 134 proteins were upregulated and 561 were downregulated in HN2-exposed tissues relative to DMSO-treated control tissues, with several complement proteins significantly upregulated. Protein enrichment and protein-protein interaction analyses identified the complement pathway as the most significantly enriched pathway in mouse ear skin 24 h after HN2 exposure. ELISA analysis of protein extracts confirmed increased levels of complement factor B, complement C3a, complement C5a, and complement C5b-9, also known as the membrane attack complex. Taken together, these data suggest that activation of the complement pathway may represent a novel target for vesicant countermeasure development.
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BibTeX
@article{mao2026investigation,
title = {{Investigation of inflammatory mechanisms induced by mechlorethamine in mouse ear.}},
author = {Ganming Mao and Ruchita Bhavsar and Trishaal Janardhanam Raghavendra Rao and Haiyan Zheng and Caifeng Zhao and Milankumar Prajapati and Blase Billack},
journal = {Current research in toxicology},
year = {2026},
month = oct,
doi = {10.1016/j.crtox.2026.100321},
url = {https://europepmc.org/article/MED/42898616},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Investigation of inflammatory mechanisms induced by mechlorethamine in mouse ear.
AU - Ganming Mao
AU - Ruchita Bhavsar
AU - Trishaal Janardhanam Raghavendra Rao
AU - Haiyan Zheng
AU - Caifeng Zhao
AU - Milankumar Prajapati
AU - Blase Billack
PY - 2026
DA - 2026/10/04
JO - Current research in toxicology
DO - 10.1016/j.crtox.2026.100321
UR - https://europepmc.org/article/MED/42898616
AB - Mechlorethamine (HN2) is toxic to the skin and causes inflammation accompanied by disruption of the dermal-epidermal junction (DEJ), commonly known as vesication. HN2 is a sulfur mustard mimic used in research settings to investigate the pharmaco-toxic effects of vesicants. Effective medical countermeasures for vesicant-induced injury remain limited, underscoring the need to identify novel targets for reducing vesication. The present study used HN2 dissolved in dimethyl sulfoxide (DMSO) to induce mouse ear edema and investigate the contribution of the complement system (CS) to skin responses 24 h after exposure to HN2, with DMSO serving as the vehicle control. Tissues were homogenized and processed for proteomic analysis to examine the protein milieu in skin actively responding to HN2-mediated cutaneous injury. Comparative analysis identified 695 proteins that were differentially expressed between the vehicle- and HN2-treated groups (p < 0.05, fold change ≥1). Of these, 134 proteins were upregulated and 561 were downregulated in HN2-exposed tissues relative to DMSO-treated control tissues, with several complement proteins significantly upregulated. Protein enrichment and protein-protein interaction analyses identified the complement pathway as the most significantly enriched pathway in mouse ear skin 24 h after HN2 exposure. ELISA analysis of protein extracts confirmed increased levels of complement factor B, complement C3a, complement C5a, and complement C5b-9, also known as the membrane attack complex. Taken together, these data suggest that activation of the complement pathway may represent a novel target for vesicant countermeasure development.
SN - 2666-027X
ER -