|
|
|
Grant marks breakthrough in equine heaves
Press Release 22nd November 2006
A grant from The Horse Trust has led to a breakthrough in the lung function
analysis of horses subject to equine heaves the horse equivalent of human asthma -
and which may ultimately lead to better prevention and treatment for potential victims.
Equine heaves (also termed recurrent airway obstruction - RAO) shares many similarities
with human occupational dust induced asthma. It is a chronic obstructive pulmonary disease
(COPD) which arises typically following exposure of susceptible horses to organic dust from
poor quality hay and straw.
Mast cells, which are found throughout the body, store and release inflammatory mediators,
such as histamine and proteases, that act on the blood vessels, smooth muscle, connective
tissue, mucous glands and inflammatory cells in response to a challenge by foreign material
(allergen). This response is believed to act as a key event in initiating and maintaining
human airway response to such challenges as occupational dust-induced asthma.
A study undertaken at the Department of Veterinary Clinical Sciences, Easter Bush Veterinary
Centre, Royal (Dick) School of Veterinary Studies, Midlothian, UK by Dr Kirstie Dacre BVMS MSc
Cert EM (Int Med) PhD, now of the Veterinary Teaching Hospital Institute of Veterinary and
Animal Biomedical Sciences, Massey University, Palmerston North, New Zealand, examined whether
equines responded to an allergen challenge in a similar way.
Tryptase, an enzyme causing mast cells to release inflammatory agents, is an indicator of biological
mast cell activity, so the aim of Dr Dacre’s study was to measure levels of mast cell tryptase in
broncholaveolar lavage fluid from control and heaves susceptible horses and to investigate the
genetic make up of equine tryptase in order to better understand its mode of action.
Dr Dacre found that the cDNA and deduced amino acid (Aa) sequences for equine tryptase shared strong
identity with other tryptases. Unusually for a trypsin-like proteinase however, equine tryptase has
alanine (2-aminopropanoic acid, a non-essential amino acid) at residue 216, rather than glycine -
the simplest of the 20 standard (proteinogenic) amino acids which confers increased arginine
substrate specificity in vitro and may restrict the dissolution of fibrinogen in the blood in vivo.
"Cloning and sequencing of the mast cell proteinase equine tryptase will allow molecular probing of
its expression in the lung of control and heaves-affected horses," Dr Dacre concluded. "Further work
is warranted to determine the biological relevance of the unique alanine 216 substitution in the
molecular sequence of the equine tryptase substrate binding pocket."
|
|
|
|
|
|
|
