Induction of Cardiac Lesions, Closely Resembling Those of Rheumatic Fever, in Rabbits Following Repeated Skin Infections With Group a Streptococci

Murphy, George E.; Swift, Homer F.

doi:10.1084/jem.89.6.687

Cited by 91 publications

(17 citation statements)

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“…Since childhood he had experienced repeated attacks of asthma and many episodes of urticaria. Allergy is probably an important causative factor in rheumatic cardiovascular disease (16,(23)(24)(25)(26)(27) and in the cardiovascular disease of disseminated lupus erythematosus (30,(57)(58)(59)(60)(61)(62)(63)(64)(65). Furthermore, it has long been known that rheumatic injury to coronary arteries occurs and in some cases leads to sclerosis of these vessels (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19); and clinico-pathologic observations indicate that injury to coronary arteries caused by disseminated lupus erythematosus also occurs and can lead to sclerosis of these arteries (66,67).…”

Section: Discussionmentioning

confidence: 99%

Experimental Induction of Athero-Arteriosclerosis by the Synergy of Allergic Injury to Arteries and Lipid-Rich Diet

1966

The Journal of Experimental Medicine

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146

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In rabbits that received a dietary supplement of cholesterol, 0.5% by weight, and concommittant injections of horse serum (group III) over a period of 80 days, coronary arterial lesions developed that in the main were different in quality and distribution from those in rabbits that received the cholesterol supplement alone (group I), and of different quality from but in distribution similar to those in rabbits that received horse serum alone (group II). Fatty lesions developed in small, rarely in medium, but never in large arteries of rabbits in group I, and these changes do not resemble coronary athero-arteriosclerosis in man. Proliferative lesions without fatty change developed in large, medium, and small arteries of rabbits in group II, and some of these closely resemble human coronary arteriosclerosis without fatty change. The changes that developed in large, medium, and small arteries of rabbits in group III were in very large majority fatty-proliferative lesions. Some of these closely resemble the changes that in some cases constitute coronary athero-arteriosclerosis in man. Nuclei with caterpillarlike chromatin pattern in longitudinal section and owl eye appearance in transverse section were observed to occur in many of the proliferating cells in thickened arterial intima in hearts of rabbits in groups II and III and in some of the lipid rich "foam" cells in arterial intima and subjacent media in hearts of rabbits in group III. Such nuclei have been observed to occur in some reacting smooth muscle cells and normal immature and reacting mature striated muscle cells of the heart. These observations indicate that at least many of the cells, including "foam" cells, in thickened intima in the experimentally induced and in naturally occurring coronary athero-arteriosclerosis are smooth muscle cells that evolved in proliferative reaction to arterial injury. Fatty change developed in aortas of the rabbits in groups I and III, and was significantly greater in group III. Results of this investigation support the hypothesis that the synergy of allergic injury to arteries and lipid-rich diet can lead to athero-arteriosclerosis.

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Section: Discussionmentioning

confidence: 99%

Experimental Induction of Athero-Arteriosclerosis by the Synergy of Allergic Injury to Arteries and Lipid-Rich Diet

1966

The Journal of Experimental Medicine

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146

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“…The remaining portion of streptococcal cells was resuspended in 0.05 M phosphate buffer, pH 6.1, containing 4% NaCl and 0.005 M EDTA with activated phage-associated lysin (13). The preparation of streptococcal protoplasts and isolation of the streptococcal membranes from this mixture was as previously described (21 solutions, these sera were prepared as follows: 500 ml of frozen fetal calf serum was thawed, heat inactivated for 30 min at 560C, distributed in 20-ml aliquots, and refrozen at -20°C until use.…”

Section: Methodsmentioning

confidence: 99%

“…In studies on experimental models of rheumatic fever in animals, a number of investigators (13,14) have emphasized the need for repeated closely spaced streptococcal inoculations with a marked cutaneous reactivity to streptococcal materials as being a prime prerequisite in inducing the pathological lesions which simulated rheumatic lesions found in man. Rantz and others (15)(16)(17)(18) have also suggested that, in man, repeated streptococcal infections are important for the disease process, and they cite the rarity of rheumatic fever before 3-4 yr of age as evidence for the necessity of an acquired hypersensitivity to streptococcal materials before rheumatic fever occurs.…”

Section: The Journal Of Clinical Investigation Volume 54 August 1974*mentioning

confidence: 99%

Cellular Reactivity Studies to Streptococcal Antigens MIGRATION INHIBITION STUDIES IN PATIENTS WITH STREPTOCOCCAL INFECTIONS AND REHEUMATIC FEVER

Read¹,

Fischetti²,

Utermohlen³

et al. 1974

J. Clin. Invest.

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A B S T R A C T The question of whether hypersensitivity to streptococcal antigens plays a role in the pathogenesis of the nonsuppurative sequelae of streptococcal infections remains at present unclear. As a first step in the approach to this question, the degree of cellular reactivity of peripheral blood leucocytes to streptococcal antigens was investigated in a number of rheumatic fever patients, patients with uncomplicated streptococcal infections, as well as normal healthy subjects.Using the in vitro technique for the inhibition of capillary migration of peripheral blood leucocytes as an index of the degree of sensitivity to streptococcal antigens, the results indicate that patients with acute rheumatic fever exhibit an exaggerated cellular reactivity to these antigens and in particular to streptococcal cell membrane antigens. This abnormal response to streptococcal membrane antigens appears to persist in rheumatic subjects for at least 5 yr after the initial 'attack of rheumatic fever. Only Group A streptococcal membrane antigens elicited this unusual response in rheumatic subjects, since the cellular reactivity to Group C and D streptococcal membranes was the same in all groups. Patients with evidence of valvular disease exhibited the same degree of cellular reactivity to these antigens as did patients without clinical evidence of rheumatic heart disease.The nature of the antigens responsible for the observed cellular response remains unknown. Enzymatic treatment of streptococcal cell walls and membranes designed to remove type-specific M proteins did not alter the observed cellular reactivity to the streptococcal antigens. The finding that an abnormal cellular response to certain streptococcal antigens is present only in rheuReceived for publication 17 July 1972 and in revised form 14 January 1974. matic patients suggests that cell-mediated factors may play an important role in the disease process. INTRODUCTICNThe question of whether hypersensitivity to hemolytic streptococci and their products might play a role in the pathogenesis of the nonsuppurative sequelae of streptococcal infections has been the subject of investigation for many years. Starting with the early work of Swift and Derick and Derick, Hitchcock, and Swift in animals (1-3), it was apparent that delayed hypersensitivity to streptococci behaved in a manner similar to that observed for tuberculin sensitivity (4). Initiation of sensitivity by prolonged focal contact between the intact bacteria and tissues of the host, inability to passively transfer streptococcal-delayed hypersensitivity with serum alone, and the lack of correlation between circulating antibodies to streptococcal products and delayed allergy were all characteristics of the streptococcal hypersensitive state (5). Apropos of these studies, several intriguing observations concerning the streptococcal hypersensitive state were made. First, repeated small inoculations of heat-killed streptococci were more effective in inducing the hypersensitive state than a single inoculation of ...

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“…Particular attention was directed at acute and serial studies of lymphocyte cell surface markers in this disorder. For some time it has been held as an established clinical principle that acute rheumatic fever is somehow related to the host immune response to the streptococcus (1)(2)(3)(4)(5)(6)(7). Whether this response is principally mediated by humoral immunity and thus the products of bone marrow-derived lymphocytes (Bcells)1 (8,9) or whether cell-mediated mechanisms operating through thymus-derived lymphocytes (T-cells) (10)(11)(12) constitute the most significant aspect of the rheumatic inflammatory response still remains to be determined.…”

Section: Introductionmentioning

confidence: 99%

Peripheral blood T and B lymphocytes during acute rheumatic fever.

Lueker¹,

Abdin²,

Williams³

1975

J. Clin. Invest.

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Induction of Cardiac Lesions, Closely Resembling Those of Rheumatic Fever, in Rabbits Following Repeated Skin Infections With Group a Streptococci

Abstract: Cardiac lesions, closely resembling those found in rheumatic fever, have developed in rabbits that sickened following multiple, successive skin infections with several serological types of group A streptococci.

Cited by 91 publications

References 8 publications

Experimental Induction of Athero-Arteriosclerosis by the Synergy of Allergic Injury to Arteries and Lipid-Rich Diet

Experimental Induction of Athero-Arteriosclerosis by the Synergy of Allergic Injury to Arteries and Lipid-Rich Diet

Cellular Reactivity Studies to Streptococcal Antigens MIGRATION INHIBITION STUDIES IN PATIENTS WITH STREPTOCOCCAL INFECTIONS AND REHEUMATIC FEVER

Peripheral blood T and B lymphocytes during acute rheumatic fever.

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