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Viral-Antibody Complexes in Canine Adenovirus Type I (CAV-1) Ocular Lesion: Leukocyte Chemotaxis and Enzyme Release

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Viral-Antibody Complexes in Canine Adenovirus Type I (CAV-1) Ocular Lesion: Leukocyte Chemotaxis and Enzyme Release University of Pennsylvania ScholarlyCommons Departmental Papers (Vet) School of Veterinary Medicine 7-1-1975 Viral-Antibody Complexes in Canine Adenovirus Type I (CAV-1) Ocular Lesion: Leukocyte Chemotaxis and Enzyme Release Leland E. Carmichael B. L. Medic Stephen I. Bistner Gustavo D. Aguirre University of Pennsylvania Follow this and additional works at: https://repository.upenn.edu/vet_papers Part of the Ophthalmology Commons, and the Veterinary Medicine Commons Recommended Citation Carmichael, L. E., Medic, B. L., Bistner, S. I., & Aguirre, G. D. (1975). Viral-Antibody Complexes in Canine Adenovirus Type I (CAV-1) Ocular Lesion: Leukocyte Chemotaxis and Enzyme Release. Cornell Veterinarian, 65 (3), 331-351. Retrieved from https://repository.upenn.edu/vet_papers/29 At the time of publication, author Gustavo D. Aguirre was affiliated with theeterinar V y Virus Research Institute at Cornell University. Currently, he is a faculty member at Penn Vet at the University of Pennsylvania. PMID: 1095299 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/vet_papers/29 For more information, please contact [email protected]. Viral-Antibody Complexes in Canine Adenovirus Type I (CAV-1) Ocular Lesion: Leukocyte Chemotaxis and Enzyme Release Abstract Canine adenovirus-type 1 (CAV-1)-antibody complexes caused severe anterior uveitis with corneal edema ("blue eye") when injected into the anterior chamber of normal dogs. The response of the anterior uvea to such immune complexes (IC) was similar to the spontaneously occurring disease. In the presence of complement (C'), IC caused release of neutrophile chemotactic factors. Following phagocytosis of IC-C', leukocytes released lysosomal enzymes, as indicated by the presence of acid phosphatase in the surrounding medium. Membrane bound viral aggregates, presumably IC, were common in neutrophiles and in macrophages that had infiltrated the anterior chamber of opaque eyes that occurred after intravenous (IV) inoculation with attenuated CAV-1. These data were incorporated into a postulated scheme for the pathogenesis of CAV-1 uveitis with corneal edema. Disciplines Medicine and Health Sciences | Ophthalmology | Veterinary Medicine Comments At the time of publication, author Gustavo D. Aguirre was affiliated with theeterinar V y Virus Research Institute at Cornell University. Currently, he is a faculty member at Penn Vet at the University of Pennsylvania. PMID: 1095299 This journal article is available at ScholarlyCommons: https://repository.upenn.edu/vet_papers/29 330 R. A. ARGENZIO 77. Schultz, S. G. and P. F. Curran. 1968. Intestinal absorption of sodium chlo~ide and water. Hand~ook of Physiology, Alimentary Canal, Washmgton, D.C.: Am. PhyS101. Soc., Sect. 6, Vol. III, Chapt. 66, p. 1245-1275. 78. Shehadek, Z., R. M. Grantham, G. A. Brecher and E. D. Jacobson. VIRAL-ANTIBODY COMPLEXES IN CANINE 1969. The effects of infusion rate and osmolality on volumogenic diarrhea. Gastroenterology, 57:24-29. 79. Slade, L. M., R. Bishop, J. G. Morris and D. G. Robinson. 1969. Di­ ADENOVIRUS' TYPE 1 (CAV-I) gestion and absorption of 15N-Iabelled microbial protein in the large intestine of the horse. Brit. Vet. J. 127:xii-xiii. OCULAR LESIONS: 80. Slade, L. M., D. G. Robinson and K. E. Casey. 1970. Nitrogen metabolism in non-ruminant herbivores. 1. The influence of non. LEUKOCYTE CHEMOTAXIS protein nitrogen and protein quality on nitrogen retention of adult mares. J. Anim. Sci. 130:753-760. 81. Svendsen, P. and B. Kristensen. 1970. Cecal dilatation in cattle. AND ENZYME RELEASE Nord. Vet. Med. 22: 578-583. 82. Svendsen, P. 1972. Inhibition of cecal motility in sheep by volatile L. E. CARMICHAEL!, B. L. S. MEDICi, S. 1. BISTNER2, fatty acids. Nord. Vet. Med. 24 :393.401. and G. D. AGUIRREl 83. Swallow, J. H. and C. F. Code. 1964. Intestinal transmucosal fluxes of bicarbonate. Am. J. Physiol. 212:717·723. 1Veterinary Virus Research Institute 84. Tietz, W. J. 1970. Autonomic nervous system. In: Duke's Physiology and 2Department of Small Animal M edicine and Surgery (Bistner), of Domestic Animals, ed. by M. J. Swenson. Ithaca: Comstock, New York State Veterinary College, Chapt. 48, p. 1082·1118. Cornell Unive?'sity, Ithaca, N.Y. 14853 85. Turnberg, L. A., F. A. Bieberdorf, S. G. Morawski and J. S. Ford­ tran. 1970. Interrelationships of chloride, bicarbonate, sodium, and Accepted October 24, J974 hydrogen transport in the human ileum. J. Clin. Invest. 49: 557.567. 86. Windgate, D. L., E. Krag, H . S. Mekhjian, and S. F. Phillips. 1973. Relationships between ion and water movement in the human jejunum, ileum and colon during perfusion with bile acids. Clin. Sci. Mol. Med. 45 :593-606. ABSTRACT Canine adenovirus-type 1 (CAV-l)-anti­ 87. Wootton, J. F. and R. A. Argenzio. Nitrogen utilization within the body complexes caused severe anterior uveitis with corneal equine large intestine. (submitted for publication). 88. Wrong, 0., A. Metcalfe-Gibson, R. B. 1. Morrison, S. T. Ng and A. edema ("blue eye") when injected into the anterior chamber V. Howard. 1965. In vivo dialysis of faeces as a method of stool of normal dogs. The response of the anterior uvea to such analysis. 1. Technique and Results in normal subjects. Clin. Sci. 28 :357-375. immrune complexes (IC) was similar to the spontaneously occurring disease. In the presence of complement (C/), IC caused release of neutrophile chemotactic factors. Following phagocytosis of IC-C/, leukocytes released lysosomal enzymes, as indicated by the presence of acid phosphatase in the sur­ rounding medium. Membrane bound viral aggregates, pre­ sumably IC, were common in neutrophiles and in macro­ phages that had infiltrated the anterior chamber of opaque eyes that occurred after intravenous (IV) inoculation with attenuated CAV-I. These data were incorporated into a postu­ lated scheme for the pathogenesis of CAV-l uveitis with corneal edema. KEY WORDS: DOG, CANINE ADENOVIRUS-I, ANTERIOR UVEITIS, CORNEAL EDEMA, IMMUNE COMPLEX, LEUKOCYTE CHEMOTAXIS, PATHOGENESIS. (Cornell Vet., 1975, 65:331-3.51) 332 L. E. CARMICHAEL ET AL. CAV-l ANTERIOR UVEITIS 333 NFECTION by canine adenovirus type-l (CAV-l) causes a into the anterior chamber and trabecular spaces. The inflam­ I generalized, frequently fatal disease in young dogs; how­ matory cells, consisting of mononuclear and somewhat fewer ever the disease in older animals usually is mild, often being numbers of polymorphonuclear leukocytes, occurred as clust­ recognized only by an increase in specific antibody or by the ers within a fibrin meshwork (keratic precipitates) and com­ appearance in recovered dogs of severe inflammation of the monly were found closely adherent to the corneal endothelium. anterior uvea and corneal edema ("blue eye"). Ocular mani­ Electron microscopic study revealed phagocytized aggregates festations also are seen following vaccination with attenuated of membrane-bound CAV-l particles within the cytoplasm of CAV-l strains (4,9). Previous reports from this laboratory apparently normal and degenerating macrophages and neu­ (1,5,6) have described clinical and pathological features of the trophiles. Such aggregates were interpreted as IC within ocular disease in relation to changes associated with viral phagolysosomes. growth in the eye and the associated systemic and local im­ To further investigate the pathogenic functions of IC in mune responses. It was hypothecated that the ocular lesions CA V -locular disease, the generation of leukocytic chemotac­ were mainly a consequence of Type III (immune complex­ tic factors (CF) and release of lysosomal hydrolases as pos­ mediated) hypersensitivity, for a feature of the disease was sible mediators of corneal endothelial injury were examined. the demonstration of viral antigen and specific antibody in I n this paper, additional evidence is presented that indicates the anterior uveal tracts of virtually all affected eyes. Also, a pathogenetic role for viral-antibody complexes in the an­ severe uveitis occurred after the intraocular injection of terior uvea of dogs infected with CA V -1. In addition to ac­ canine adenoviral-antibody complexes (immune complexes). counting for the sudden and extensive accumulations of in­ Inflammatory responses were more severe if complement flammatory cells in the anterior chamber and trabecular (C') had been added to immune complex (IC) preparations spaces of affected eyes, in vivo and in vitro studies were made before injections were made. Extensive and severe panuveitis to attempt to relate lysosomal enzyme release to corneal also occurred within 4 hours following intravitreous inj ection endothelial damage. of non-living CAV-I soluble antigens into eyes of immunized dogs with high levels of complement-fixing and neutralizing MATERIALS AND METHODS CAV-l antibodies. In the latter instances, histological exam­ Immune complex pTcpaTations. Cornell-l strain CAV-l ination of affected eyes indicated that recovery would not have (infectious canine hepatitis virus) was used. Methods of virus occurred. isolation, growth in dog kidney cell (DKC) cultures, and the In a recent study (I), ultrastructural changes were de­ preparation of viral antigens have been described (5,6). Im­ scribed in the corneal endothelium of dogs at various times mune complex preparations were made as reported previous­ during the course of experimental CAV-l infection. During ly (6), however in some experiments dissociated viral anti­ the early stage of inapparent or mild luveitis, virus could be gens were prepared by a methanol precipitation
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