Alternate Pathway Activation of Complement in a Proteus mirabilis Ulceration of the Cornea

Mondino, Bartly J.; Brown, Stuart I.; Rabin, Bruce S.; Bruno, Jorge

doi:10.1001/archopht.1978.03910060285021

Cited by 20 publications

(9 citation statements)

References 8 publications

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“…The human cornea contains hemolytic complement [5,8] which may play a role in bacterial keratitis [9], Additionally, elevated levels of complement in tears from eyes with corneal ulcers may contribute to host defense of the cornea against invading pathogens. Important functions of comple ment in host defense against bacteria include chemotaxis of polymorphonuclear leukocytes, immune adherence facilitating phagocytosis, anaphylatoxin activity causing increased vascular permeability and cytolysis of bacteria.…”

Section: Discussionmentioning

confidence: 43%

Hemolytic Complement in Tears

Mondino

Zaidman

1983

Ophthalmic Res

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We performed hemolytic assays for C1, C4, C3 and C5 on tear samples from 7 normal subjects and 10 patients with corneal ulcers. Hemolytic activities in tears were determined by 50% hemolysis of sensitized sheep red blood cells. Absent or low hemolytic activities of C1, C4 and C3 were found in normal tears. C5 was detected in tear samples from 4 of 7 normal subjects. Tear samples from patients with corneal ulcers showed elevated levels of C1, C4, C3 and C5, but wide ranges in values were found. C5 had the highest hemolytic activities in both normal tears and tears from eyes with corneal ulcers. Complement in tears may contribute to host defense in microbial corneal ulcers.

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Section: Discussionmentioning

confidence: 43%

Hemolytic Complement in Tears

Mondino

Zaidman

1983

Ophthalmic Res

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“…In the present paper, further in vivo and in vitro parameters which have been investigated in our laboratory were chosen to elaborate structure/ activity relationships of the lipid A analogs of the 400 and 500 series. The parameters were as follows: (I) the four bone marrow cell reactions elicited by endotoxin in mice (51,(53)(54)(55)(56), i.e., 1) cytotoxicity for bone marrow cells, as an expression of necrotic alterations, 2) decrease in nucleated cell numbers, an eventual manifestation of leukocyte migration from the marrow into the periphery, 3) increase in red blood cell numbers, a manifestation of hemorrhage and hyperemia, 4) increased tissue thromboplastin activity (5, 6) ; (II) a skin reaction due to a single intradermal injection of endotoxin in mice (52), hemorrhage and necrosis, like the Shwartzman reaction; (III) a unique keratitis in rabbits with a corneal ring due to granulocyte migration into the cornea (31,34,35) ; (IV) hemagglutination activity of endotoxin, especially R-type endotoxin and lipid A (14). Increase of RBC Number As shown in Table 3, only analog 406 increased RBC numbers in the bone Two groups of lipid A analogs were investigated concerning some inflammatory reactions and one in vitro reaction, and structure/activity relationships were studied.…”

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confidence: 42%

Endotoxic Properties of Chemically Synthesized Lipid A Analogs

Yoshida

Hirata

Inada

et al. 1989

Microbiology and Immunology

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Biological activities of two groups of synthesized lipid A analogs, the counterpart of biosynthetic precursor, Lehmann's Ia type, 406, and E. coli lipid A type, 506, as well as their non-phosphorylated, and mono-phosphorylated analogs were investigated. The activities employed included four bone marrow cell reactions in mice, mice skin reaction, leukocytes migration in rabbits' cornea, and hemagglutination. Compound 406 and 506 elicited bone marrow reactions in mice and hemagglutination of mouse RBC, although 406 failed to elicit hemorrhage and necrosis also in mice skin. Compound 406 did not elicit corneal reaction in rabbits. The results suggest that for elicitation of this reaction and mice skin reaction, acyloxyacyl structure is required. Cytotoxicity and thromboplastin production of four bone marrow reactions had been reported by us to be endotoxic reactions, since these had not been elicited by peptidoglycan of Lactobacillus and Staphylococcus (1981) and 300 series synthetized analogs (1984) which did not have endotoxic structures. From these results, it seems that these two marrow reactions and hemagglutination require, as does the limulus test, the lipid A part structure as is present in 406.

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“…It is noteworthy that the need of ocular cells for protection has not been widely appreciated previously as there are limited data regarding the complement system in ocular disease. With the exception of ocular cicatricial pemphigoid 33–35 and bacterial keratitis, 36 only scattered reports 37–39 of the role of complement in their pathology are available.…”

Section: Discussionmentioning

confidence: 99%

Blockage of complement regulators in the conjunctiva and within the eye leads to massive inflammation and iritis

et al. 2001

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SUMMARYThe open environment of the eye is continuously subject to an in¯ux of foreign agents that can activate complement. Decay-accelerating factor (DAF), membrane cofactor protein (MCP) and CD59 are regulators that protect self-cells from autologous complement activation on their surfaces. They are expressed in the eye at unusually high levels but their physiological importance in this site is unstudied. In the rat, a structural analogue termed 5I2 antigen (5I2 Ag) has actions overlapping DAF and MCP. In this investigation, we injected F(abk ) 2 fragments of 5I2 mAb into the conjunctiva and aqueous humor, in the latter case with and without concomitant blockage of CD59. Massive neutrophilic in®ltration of the stroma and iris resulted upon blocking 5I2 Ag activity. Frank necrosis of the iris occurred upon concomitant intraocular blockage of CD59. C3b was identi®ed immunohistochemically, and minimal effects were seen in complement-depleted animals and in those treated with non-relevant antibody. The ®nding that blockage of 5I2 Ag function in periocular tissues and within the eye causes intense conjunctival in¯ammation and iritis demonstrates the importance of intrinsic complement regulators in protecting ocular tissues from spontaneous or bystander attack by autologous complement.

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Alternate Pathway Activation of Complement in a Proteus mirabilis Ulceration of the Cornea

Cited by 20 publications

References 8 publications

Hemolytic Complement in Tears

Hemolytic Complement in Tears

Endotoxic Properties of Chemically Synthesized Lipid A Analogs

Blockage of complement regulators in the conjunctiva and within the eye leads to massive inflammation and iritis

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