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Human sweat proteomics: Defining the proteome and elucidating potential innate immune components.

Author:

SRAVANTHY MANESH

Supervisor:

CHEW FOOK TIM

Keywords:

Sweat, 2DE-Proteome, 2D-LC-MS-MS ,Anti-bacterial, Anti-viral, Wound repair.

Date:

2009

Abstract:

The human sweat gland is differentiated into eccrine and apocrine sweat glands. The major function of eccrine sweat gland is thermoregulation during hot environments and rigorous exercise. Silver stained 2D gel by Marshal et al (1984) detected approximately 300 protein spots from healthy human sweat samples. The exact composition of proteins present in healthy human sweat still remains unclear. Studies in the elucidation of the sweat proteome will pave the way for identification and to understand the functions of sweat proteins. <br><br>This study describes an integrated approach of eccrine sweat proteome profiling using a 2DE MALDI-TOF/TOF MS and 2D-LC-MS/MS that has helped identify 98 unique proteins. By combining the two most widely used protein profiling techniques (2DE and 2D-LC-MS/MS), this study has achieved the most comprehensive characterization of the human sweat proteome till date. This study provides valuable information regarding the protein components of healthy human sweat which will pave the way for establishing the functions of sweat proteins and elucidate their role as a part of the innate defense system. Some of the proteins identified in sweat can be also used as biomarkers for diagnostic purposes.<br><br>The antimicrobial proteins deposited on to the skin via sweat act as an important part of the first line of defense against invading pathogens which prevent the pathogens from colonizing the skin and establishing an infection. This study attempted to identify the antimicrobial proteins present in healthy human sweat apart from those that have been previously reported. This lead to the identification of three novel antibacterial proteins in sweat, Superoxide dismutase 1(SOD1), Cystatin A and Lactoferrin with promising antibacterial activity against Streptococcus pyogenes, Escherichia coli and Staphylococcus epidermidis respectively. <br><br>We are exposed to a vast array of pathogens present in the environment, which includes not just bacteria but also viruses. Herpes simplex virus-1 (HSV-1) is one such virus which causes diseases on the face and skin. The impact of HSV-1 on human health globally is enormous due to its high incidence, association with immuno-compromised patients, and ability to cause recurrent disease. This study reports the presence of Cystatin A and Lactoferrin in sweat with antiviral activity against HSV-1. Studies into the mechanism of action of these proteins revealed that they inhibit important stages of HSV-1 life cycle. <br><br>This study also reports the identification of two epidermal wound repair proteins present in sweat -SOD1 and Calgranulin B. In vitro and in vivo studies have quantitatively established the wound repair function of these proteins. This study to the best of our knowledge for the first time presents the quantitative analysis of the wound repair function of these proteins.<br><br>In conclusion, this study has successfully lead to the identification of the protein composition of healthy human sweat. This study has also identified sweat proteins with antibacterial, antiviral and epidermal wound repair functions with potential applications as pharmaceutical leads. Hence, proving the presence of immune effectors in sweat and thus paving the way for the establishment of our understanding of sweat as a part of innate immune defense system.<br>

Department:

BIOLOGICAL SCIENCES

Degree Conferred:

DOCTOR OF PHILOSOPHY

Document Type:

Thesis