The study described in this thesis was designed to
examine some serological factors which may be involved
in the pathogenesis of chronic obstructive pulmonary
disease (C.O.P.D.) of horses.
In the first section, zone electrophoresis of
normal horse serum on agarose gels (pH 8.6) was studied
and the serum electrophoretic profiles of normal and
C.O.P.D. affected horses and ponies were compared. No
differences between the serum electrophoretic profiles
of healthy and C.O.P.D. affected horses and ponies were
observed which could be attributed to the presence of the
disease.
In the second section, the nature of the two
major, electrophoretically distinct antiproteases in
horse serum was investigated prior to examining the
possible association of antiprotease deficiency with
the onset of C.O.P.D. in the horse, analogous to the
association of the inherited dysproteinaemia of alpha-1
antitrypsin deficiency and chronic lung disease in
man. The electrophoretically faster antiprotease, a
functional homologue of human alpha-1 antitrypsin, was
shown to appear in the prealbumin region of horse serum
after acidic starch gel electrophoresis (pH 4.3). This
polymorphic antiprotease corresponded to the allele
products of the Pr locus of horse serum described by
Braend (1970). The genetically determined polymorphism
of the Pr antiprotease was examined by acid starch
gel electrophoresis, isoelectric focusing and immunofixation
electrophoresis. The occurrence of a second
antiprotease in the acidic prealbumin region of horse
serum was postulated, although its nature remains to
be established.
The electrophoretically slower antiprotease of
horse serum was identified as alpha-2 macroglobulin,
and was shown to contribute 48 percent of the total
serum antiproteolytic activity. As in man, horse
alpha-2 macroglobulin is able to inhibit the proteolytic
activity of trypsin, but has only limited inhibitory
activity on its esterolytic activity. Native alpha-2
macroglobulin was shown to possess esterase activity
and the possible association of the macroglobulin and
plasma pseudocholinesterase is discussed. No inherited
polymorphism of horse alpha-2 macroglobulin was observed.
The Pr antiprotease allele frequencies in healthy
and C.O.P.D. affected Thoroughbred horses were compared
and no significant differences were observed. There
was however an apparently increased frequency of the
PrW allele amongst C.O.P.D. affected horses and ponies
of mixed breeding, although the significance of this
observation could not be established. Significantly
increased levels of immunochemically measured circulating
Pr protein were observed in a C.O.P.D. affected
population, although no corresponding increase in
biochemically measured serum trypsin inhibitory
capacity (STIC) was observed in this same population.
It was concluded that serum antiprotease deficiency
and consequent predisposition to the development of
C.O.P.D. was unlikely to occur in the horse, although
a possible deficiency of local bronchiolar antiproteases,
resulting in an increased chance of hypersensitization
to the protease antigens of the fungi
commonly incriminated in C .0 .P .D ., could not be excluded.
In the third section the occurrence of a serum
homocytotropic antibody in the horse, homologous to
human IgE, was investigated. A passively transferable
homocytotropic antibody against Culicoides pulicaris
was demonstrated in the serum of horses and ponies
affected with recurrent seasonal dermatitis. Like
human IgE, this antibody is heat-labile, susceptible
to thiol reducing agents and persists for long periods
in homologous skin. The elution characteristics of
the horse antibody on DEAE-anion exchange chromatography
are similar to those of human IgE. Anti-human
IgE was shown to induce reversed anaphylaxis-like
reactions in horse skin and immunfluorescent studies
provided preliminary evidence of the binding of antihuman
IgE to horse mast cells. These observations
on the equine homocytotropic antibody satisfy Vaerman's
(1970) criteria of interspecies protein homology
suggesting that the antibody is homologue of human IgE.
