Onchocerciasis: Infection with nematodes of the genus ONCHOCERCA. Characteristics include the presence of firm subcutaneous nodules filled with adult worms, PRURITUS, and ocular lesions.Onchocerciasis, Ocular: Filarial infection of the eyes transmitted from person to person by bites of Onchocerca volvulus-infected black flies. The microfilariae of Onchocerca are thus deposited beneath the skin. They migrate through various tissues including the eye. Those persons infected have impaired vision and up to 20% are blind. The incidence of eye lesions has been reported to be as high as 30% in Central America and parts of Africa.Onchocerca: A genus of parasitic nematodes whose organisms live and breed in skin and subcutaneous tissues. Onchocercal microfilariae may also be found in the urine, blood, or sputum.Onchocerca volvulus: A species of parasitic nematodes widely distributed throughout central Africa and also found in northern South America, southern Mexico, and Guatemala. Its intermediate host and vector is the blackfly or buffalo gnat.Ivermectin: A mixture of mostly avermectin H2B1a (RN 71827-03-7) with some avermectin H2B1b (RN 70209-81-3), which are macrolides from STREPTOMYCES avermitilis. It binds glutamate-gated chloride channel to cause increased permeability and hyperpolarization of nerve and muscle cells. It also interacts with other CHLORIDE CHANNELS. It is a broad spectrum antiparasitic that is active against microfilariae of ONCHOCERCA VOLVULUS but not the adult form.Simuliidae: Several species of the genus Simulium (family Simuliidae) that act as intermediate hosts (vectors) for the parasitic disease ONCHOCERCIASIS.Filaricides: Pharmacological agents destructive to nematodes in the superfamily Filarioidea.Microfilaria: The prelarval stage of Filarioidea in the blood and other tissues of mammals and birds. They are removed from these hosts by blood-sucking insects in which they metamorphose into mature larvae.Antiparasitic Agents: Drugs used to treat or prevent parasitic infections.Skin Diseases, Parasitic: Skin diseases caused by ARTHROPODS; HELMINTHS; or other parasites.Mansonelliasis: Infection with nematodes of the genus MANSONELLA. Symptoms include pruritus, headache, and articular swelling.Antinematodal Agents: Substances used in the treatment or control of nematode infestations. They are used also in veterinary practice.Diethylcarbamazine: An anthelmintic used primarily as the citrate in the treatment of filariasis, particularly infestations with Wucheria bancrofti or Loa loa.Africa, Western: The geographical area of Africa comprising BENIN; BURKINA FASO; COTE D'IVOIRE; GAMBIA; GHANA; GUINEA; GUINEA-BISSAU; LIBERIA; MALI; MAURITANIA; NIGER; NIGERIA; SENEGAL; SIERRA LEONE; and TOGO.Loiasis: A parasitic infection caused by the nematode Loa loa. The vector in the transmission of this infection is the horsefly (Tabanus) or the deerfly or mango fly (Chrysops). The larvae may be seen just beneath the skin or passing through the conjunctiva. Eye lesions are not uncommon. The disease is generally mild and painless.Loa: A genus of parasitic nematodes found throughout the rain-forest areas of the Sudan and the basin of the Congo. L. loa inhabits the subcutaneous tissues, which it traverses freely.Anthelmintics: Agents destructive to parasitic worms. They are used therapeutically in the treatment of HELMINTHIASIS in man and animal.Antigens, Helminth: Any part or derivative of a helminth that elicits an immune reaction. The most commonly seen helminth antigens are those of the schistosomes.Liberia: A republic in western Africa, south of GUINEA and east of COTE D'IVOIRE. Its capital is Monrovia.Cameroon: A republic in central Africa lying east of CHAD and the CENTRAL AFRICAN REPUBLIC and west of NIGERIA. The capital is Yaounde.Antibodies, Helminth: Immunoglobulins produced in a response to HELMINTH ANTIGENS.Guinea: A republic in western Africa, south of SENEGAL and MALI, east of GUINEA-BISSAU. Its capital is Conakry.Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body.Eye Diseases: Diseases affecting the eye.Endemic Diseases: The constant presence of diseases or infectious agents within a given geographic area or population group. It may also refer to the usual prevalence of a given disease with such area or group. It includes holoendemic and hyperendemic diseases. A holoendemic disease is one for which a high prevalent level of infection begins early in life and affects most of the child population, leading to a state of equilibrium such that the adult population shows evidence of the disease much less commonly than do children (malaria in many communities is a holoendemic disease). A hyperendemic disease is one that is constantly present at a high incidence and/or prevalence rate and affects all groups equally. (Last, A Dictionary of Epidemiology, 3d ed, p53, 78, 80)Insect Control: The reduction or regulation of the population of noxious, destructive, or dangerous insects through chemical, biological, or other means.Togo: A republic in western Africa, lying between GHANA on its west and BENIN on its east. Its capital is Lome.Neglected Diseases: Diseases that are underfunded and have low name recognition but are major burdens in less developed countries. The World Health Organization has designated six tropical infectious diseases as being neglected in industrialized countries that are endemic in many developing countries (HELMINTHIASIS; LEPROSY; LYMPHATIC FILARIASIS; ONCHOCERCIASIS; SCHISTOSOMIASIS; and TRACHOMA).EcuadorSierra Leone: A republic in western Africa, south of GUINEA and west of LIBERIA. Its capital is Freetown.Optic Atrophy: Atrophy of the optic disk which may be congenital or acquired. This condition indicates a deficiency in the number of nerve fibers which arise in the RETINA and converge to form the OPTIC DISK; OPTIC NERVE; OPTIC CHIASM; and optic tracts. GLAUCOMA; ISCHEMIA; inflammation, a chronic elevation of intracranial pressure, toxins, optic nerve compression, and inherited conditions (see OPTIC ATROPHIES, HEREDITARY) are relatively common causes of this condition.Eye: The organ of sight constituting a pair of globular organs made up of a three-layered roughly spherical structure specialized for receiving and responding to light.Central African Republic: A republic in central Africa south of CHAD and SUDAN, north of DEMOCRATIC REPUBLIC OF THE CONGO, and east of CAMEROON. The capital is Bangui.Blindness: The inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of EYE DISEASES; OPTIC NERVE DISEASES; OPTIC CHIASM diseases; or BRAIN DISEASES affecting the VISUAL PATHWAYS or OCCIPITAL LOBE.Nigeria: A republic in western Africa, south of NIGER between BENIN and CAMEROON. Its capital is Abuja.Elephantiasis, Filarial: Parasitic infestation of the human lymphatic system by WUCHERERIA BANCROFTI or BRUGIA MALAYI. It is also called lymphatic filariasis.Ocular Hypertension: A condition in which the intraocular pressure is elevated above normal and which may lead to glaucoma.Insect Vectors: Insects that transmit infective organisms from one host to another or from an inanimate reservoir to an animate host.Parasite Load: Measure of the number of the PARASITES present in a host organism.Mebendazole: A benzimidazole that acts by interfering with CARBOHYDRATE METABOLISM and inhibiting polymerization of MICROTUBULES.Disease Eradication: Termination of all transmission of infection by global extermination of the infectious agent through surveillance and containment (From Porta, A Dictionary of Epidemiology, 5th ed).AfricaTropical Medicine: The branch of medicine concerned with diseases, mainly of parasitic origin, common in tropical and subtropical regions.Mali: A country in western Africa, east of MAURITANIA and south of ALGERIA. Its capital is Bamako. From 1904-1920 it was known as Upper Senegal-Niger; prior to 1958, as French Sudan; 1958-1960 as the Sudanese Republic and 1959-1960 it joined Senegal in the Mali Federation. It became an independent republic in 1960.Gift Giving: The bestowing of tangible or intangible benefits, voluntarily and usually without expectation of anything in return. However, gift giving may be motivated by feelings of ALTRUISM or gratitude, by a sense of obligation, or by the hope of receiving something in return.Toxoplasmosis, Ocular: Infection caused by the protozoan parasite TOXOPLASMA in which there is extensive connective tissue proliferation, the retina surrounding the lesions remains normal, and the ocular media remain clear. Chorioretinitis may be associated with all forms of toxoplasmosis, but is usually a late sequel of congenital toxoplasmosis. The severe ocular lesions in infants may lead to blindness.Filariasis: Infections with nematodes of the superfamily FILARIOIDEA. The presence of living worms in the body is mainly asymptomatic but the death of adult worms leads to granulomatous inflammation and permanent fibrosis. Organisms of the genus Elaeophora infect wild elk and domestic sheep causing ischemic necrosis of the brain, blindness, and dermatosis of the face.Wolbachia: A genus of bacteria comprised of a heterogenous group of gram-negative small rods and coccoid forms associated with arthropods. (From Bergey's Manual of Systematic Bacteriology, vol 1, 1984)Ghana: A republic in western Africa, south of BURKINA FASO and west of TOGO. Its capital is Accra.Filarioidea: A superfamily of nematodes of the suborder SPIRURINA. Its organisms possess a filiform body and a mouth surrounded by papillae.DNA, Helminth: Deoxyribonucleic acid that makes up the genetic material of helminths.Dipetalonema: A filarial nematode parasite of mammalian blood with the vector being a tick or small fly.Diptera: An order of the class Insecta. Wings, when present, number two and distinguish Diptera from other so-called flies, while the halteres, or reduced hindwings, separate Diptera from other insects with one pair of wings. The order includes the families Calliphoridae, Oestridae, Phoridae, SARCOPHAGIDAE, Scatophagidae, Sciaridae, SIMULIIDAE, Tabanidae, Therevidae, Trypetidae, CERATOPOGONIDAE; CHIRONOMIDAE; CULICIDAE; DROSOPHILIDAE; GLOSSINIDAE; MUSCIDAE; TEPHRITIDAE; and PSYCHODIDAE. The larval form of Diptera species are called maggots (see LARVA).Schistosomiasis: Infection with flukes (trematodes) of the genus SCHISTOSOMA. Three species produce the most frequent clinical diseases: SCHISTOSOMA HAEMATOBIUM (endemic in Africa and the Middle East), SCHISTOSOMA MANSONI (in Egypt, northern and southern Africa, some West Indies islands, northern 2/3 of South America), and SCHISTOSOMA JAPONICUM (in Japan, China, the Philippines, Celebes, Thailand, Laos). S. mansoni is often seen in Puerto Ricans living in the United States.Parasitic Diseases: Infections or infestations with parasitic organisms. They are often contracted through contact with an intermediate vector, but may occur as the result of direct exposure.Mansonella: A genus of parasitic nematodes whose organisms are distributed in Central and South America. Characteristics include a smooth cuticle and an enlarged anterior end.Communicable Disease Control: Programs of surveillance designed to prevent the transmission of disease by any means from person to person or from animal to man.Anterior Chamber: The space in the eye, filled with aqueous humor, bounded anteriorly by the cornea and a small portion of the sclera and posteriorly by a small portion of the ciliary body, the iris, and that part of the crystalline lens which presents through the pupil. (Cline et al., Dictionary of Visual Science, 4th ed, p109)Iridocyclitis: Acute or chronic inflammation of the iris and ciliary body characterized by exudates into the anterior chamber, discoloration of the iris, and constricted, sluggish pupil. Symptoms include radiating pain, photophobia, lacrimation, and interference with vision.Cornea: The transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous CORNEAL EPITHELIUM; BOWMAN MEMBRANE; CORNEAL STROMA; DESCEMET MEMBRANE; and mesenchymal CORNEAL ENDOTHELIUM. It serves as the first refracting medium of the eye. It is structurally continuous with the SCLERA, avascular, receiving its nourishment by permeation through spaces between the lamellae, and is innervated by the ophthalmic division of the TRIGEMINAL NERVE via the ciliary nerves and those of the surrounding conjunctiva which together form plexuses. (Cline et al., Dictionary of Visual Science, 4th ed)GuatemalaNiridazole: An antischistosomal agent that has become obsolete.Corneal Opacity: Disorder occurring in the central or peripheral area of the cornea. The usual degree of transparency becomes relatively opaque.Uganda: A republic in eastern Africa, south of SUDAN and west of KENYA. Its capital is Kampala.Americas: The general name for NORTH AMERICA; CENTRAL AMERICA; and SOUTH AMERICA unspecified or combined.Necatoriasis: Infection of humans or animals with hookworms of the genus NECATOR. The resulting anemia from this condition is less severe than that from ANCYLOSTOMIASIS.
OnchocerciasisOnchocerca tubingensis: Onchocerca tubingensis is the name of a nematode.The Free Dictionary It was 1974 discovered and published by O.Onchocerca volvulus: Onchocerca volvulus is a nematode that causes onchocerciasis or "river blindness" mostly in Africa. Long-term corneal inflammation, or keratitis, leads to thickening of the corneal stroma which ultimately leads to blindness.ATCvet code QP54: ==QP54A Macrocyclic lactones==IvermectinAntinematodal agent: An antinematodal agent is a type of anthelmintic designed to reduce nematode infection.DiethylcarbamazineLoa loa filariasisATCvet code QP52: ==QP52A Anthelmintics==Global Bank Liberia: Global Bank Liberia Limited (GBLL), commonly referred to as Global Bank Liberia, is a commercial bank in Liberia. It is one of the commercial banks licensed by the Central Bank of Liberia, the national banking regulator.Cameroon–China relations: China and Cameroon established bilateral relations on March 26, 1971. Cameroon is an adherent to the One China Policy.Transport in Guinea: The railway from Conakry to Kankan ceased operating in the mid-1980s. Domestic air services are intermittent.Chorioretinitis: Chorioretinitis is an inflammation of the choroid (thin pigmented vascular coat of the eye) and retina of the eye. It is a form of posterior uveitis.Neuro-ophthalmology: Neuro-ophthalmology is an academically-oriented subspecialty that merges the fields of neurology and ophthalmology, often dealing with complex systemic diseases that have manifestations in the visual system. Neuro-ophthalmologists initially complete a residency in either neurology or ophthalmology, then do a fellowship in the complementary field.Theodor Bilharz Research Institute: The Theodor Bilharz Research Institute is located in Giza, Egypt.Pugo and Togo: Pugo and Togo were a Filipino comedy team in Philippine movies during the 1940s up to the 1950s.Pugo, movie-industry.KPC Medical College and HospitalSmoking in Ecuador: Smoking in Ecuador is more common among men and younger people. More than half of Ecuadorian smokers desire to quit.Index of Sierra Leone-related articles: Articles (arranged alphabetically) related to Sierra Leone include:Berk–Tabatznik syndrome: Berk–Tabatznik syndrome is a condition with an unknown cause that shows symptoms of short stature, congenital optic atrophy and brachytelephalangy. This condition is extremely rare with only two cases being found.Guiding Eyes for the Blind: Yorktown Heights, New YorkReligion in the Central African Republic: According to 2010 estimates, about 80 percent of the population of the Central African Republic are Christians. Islam is practiced by 15 percent of the population.Blind People's Association: The Blind People’s Association (BPA) is an organisation in India which promotes comprehensive rehabilitation of persons with all categories of disabilities through education, training, employment, community based rehabilitation, integrated education, research, publications, human resource development and other innovative means.Nigerian Ports Authority: The Nigerian Ports Authority (NPA) is a federal government agency that governs and operates the ports of Nigeria. The major ports controlled by the NPA include: the Lagos Port Complex and Tin Can Island Port in Lagos; Calabar Port, Delta Port, Rivers Port at Port Harcourt, and Onne Port.LevobetaxololMebendazoleMIM Pan-African Malaria Conference 2009Tulane University School of Public Health and Tropical Medicine: The Tulane School of Public Health and Tropical Medicine is part of Tulane University of the U.S.Papa MaliGift registry: A gift registry is a particular type of wish list.Cytoplasmic incompatibility: Cytoplasmic incompatibility (CI) is a phenomenon that results in sperm and eggs being unable to form viable offspring. The effect arises from changes in the gamete cells caused by intracellular parasites like Wolbachia, which infect a wide range of insect species.Health in Ghana: Health in Ghana includes the healthcare systems on prevention, care and treatment of diseases and other maladies.Filarioidea: The Filarioidea are a superfamily of nematodes (roundworms). The members of this superfamily are known as filarial worms.Acanthocheilonema viteae: DescriptionChrysomya albiceps: Chrysomya albiceps is a species belonging to the blow fly family, Calliphoridae. It is of great medical and sanitary importance, being associated with myiasis in Africa and America although it plays a more significant role as a predator of other dipteran larvae.SchistosomiasisParasitic disease: A parasitic disease is an infectious disease caused or transmitted by a parasite. Many parasites do not cause diseases.Mansonella ozzardi: Mansonella ozzardi is a parasite in the phylum of Nematoda. This filarial nematode is one of two that causes serous cavity filariasis in humans.Saal Greenstein syndrome: Saal Greenstein syndrome is a very rare autosomal recessive genetic disorder characterized by stunted growth, short limbs, microcephaly, and an anomalous cleavage of the anterior chamber of the eye. The disorder is similar to Robinow syndrome except for anterior chamber anomalies and, in one case, hydrocephalus.Fuchs heterochromic iridocyclitis: Fuchs heterochromic iridocyclitis (FHI) is a chronic unilateral uveitis appearing with the triad of heterochromia, predisposition to cataract and glaucoma, and keratitic precipitates on the posterior corneal surface. Patients are often asymptomatic and the disease is often discovered through investigation of the cause of the heterochromia or cataract.Guatemala syphilis experiment: The syphilis experiments in Guatemala were United States-led human experiments conducted in Guatemala from 1946 to 1948, during the administration of President Truman and President Juan José Arévalo with the cooperation of some Guatemalan health ministries and officials. Doctors infected soldiers, prostitutes, prisoners and mental patients with syphilis and other sexually transmitted diseases, without the informed consent of the subjects, and treated most subjects with antibiotics.NiridazoleKramers' opacity law: Kramers' opacity law describes the opacity of a medium in terms of the ambient density and temperature, assuming that the opacity is dominated by bound-free absorption (the absorption of light during ionization of a bound electron) or free-free absorption (the absorption of light when scattering a free ion, also called bremsstrahlung).Phillips (1999), p.Makerere University School of Medicine
(1/68) Distribution of the blinding and nonblinding strains of Onchocerca volvulus in Nigeria.
Onchocerciasis remains an important public health problem throughout much of sub-Saharan Africa. Nigeria is the country whose population is most afflicted by onchocerciasis; however, little is known concerning the epidemiology of onchocerciasis in this country. Previous studies demonstrated that onchocerciasis in West Africa exists in two forms, which differ in their clinical and epidemiologic characteristics. This is believed to be due to the existence of 2 strains of Onchocerca volvulus, the causative agent of onchocerciasis. The O-150 polymerase chain reaction has been developed to differentiate these 2 strains, and this method has been used to map the distribution of the blinding and nonblinding strains of O. volvulus in Nigeria. The strain distribution is consistent with what is known concerning the ecology and epidemiology of onchocerciasis in this country. The results also suggest that migration may be affecting the historic distribution of the 2 strains of the parasite in Nigeria. (+info)
(2/68) Population biology of human onchocerciasis.
Human onchocerciasis (river blindness) is the filarial infection caused by Onchocerca volvulus and transmitted among people through the bites of the Simulium vector. Some 86 million people around the world are at risk of acquiring the nematode, with 18 million people infected and 600,000 visually impaired, half of them partially or totally blind. 99% of cases occur in tropical Africa; scattered foci exist in Latin America. Until recently control programmes, in operation since 1975, have consisted of antivectorial measures. With the introduction of ivermectin in 1988, safe and effective chemotherapy is now available. With the original Onchocerciasis Control Programme of West Africa coming to an end, both the new African Programme for Onchocerciasis Control and the Onchocerciasis Elimination Programme for the Americas, rely heavily on ivermectin self-sustained mass delivery. In consequence, the need for understanding the processes regulating parasite abundance in human and simuliid populations is of utmost importance. We present a simple mathematical framework built around recent analyses of exposure- and density-dependent processes operating, respectively, within the human and vector hosts. An expression for the basic reproductive ratio, R0, is derived and related to the minimum vector density required for parasite persistence in localities of West Africa in general and northern Cameroon in particular. Model outputs suggest that constraints acting against parasite establishment in both humans and vectors are necessary to reproduce field observations, but those in humans may not fully protect against reinfection. Analyses of host age-profiles of infection prevalence, intensity, and aggregation for increasing levels of endemicity and intensity of transmission in the Vina valley of northern Cameroon are in agreement with these results and discussed in light of novel work on onchocerciasis immunology. (+info)
(3/68) An essential role for antibody in neutrophil and eosinophil recruitment to the cornea: B cell-deficient (microMT) mice fail to develop Th2-dependent, helminth-mediated keratitis.
Invasion of the corneal stroma by neutrophils and eosinophils and subsequent degranulation disrupts corneal clarity and can result in permanent loss of vision. In the current study, we used a model of helminth-induced inflammation to demonstrate a novel role for Ab in mediating recruitment of these inflammatory cells to the central cornea. C57BL/6 and B cell-deficient (microMT) mice were immunized s. c. and injected intrastromally with Ags from the parasitic helminth Onchocerca volvulus (which causes river blindness). C57BL/6 mice developed pronounced corneal opacification, which was associated with an Ag-specific IL-5 response and peripheral eosinophilia, temporal recruitment of neutrophils and eosinophils from the limbal vessels to the peripheral cornea and subsequent migration to the central cornea. In contrast, the corneas of microMT mice failed to develop keratitis after intrastromal injection of parasite Ags unless Ags were injected with immune sera. Eosinophils were recruited from the limbal vessels to the peripheral cornea in microMT mice, but failed to migrate to the central cornea, whereas neutrophil recruitment was impaired at both stages. With the exception of IL-5, T cell responses and peripheral eosinophils were not significantly different between C57BL/6 and microMT mice. Taken together, these findings not only demonstrate that Ab is required for the development of keratitis, but also show that recruitment of neutrophils to the cornea is Ab-dependent, whereas eosinophil migration is only partially dependent upon Ab interactions. (+info)
(4/68) WHO celebrates triumph over river blindness.
(5/68) Macrofilaricidal activity of tetracycline against the filarial nematode Onchocerca ochengi: elimination of Wolbachia precedes worm death and suggests a dependent relationship.
Filarial nematodes are important and widespread parasites of animals and humans. We have been using the African bovine parasite Onchocerca ochengi as a chemotherapeutic model for O. volvulus, the causal organism of 'river blindness' in humans, for which there is no safe and effective drug lethal to adult worms. Here we report that the antibiotic, oxytetracycline is macrofilaricidal against O. ochengi. In a controlled trial in Cameroon, all adult worms (as well as microfilariae) were killed, and O. ochengi intradermal nodules resolved, by nine months' post-treatment in cattle treated intermittently for six months. Adult worms removed from concurrent controls remained fully viable and reproductively active. By serial electron-microscopic examination, the macrofilaricidal effects were related to the elimination of intracellular micro-organisms, initially abundant. Analysis of a fragment of the 16S rRNA gene from the O. ochengi micro-organisms confirmed them to be Wolbachia organisms of the order Rickettsiales, and showed that the sequence differed in only one nucleotide in 858 from the homologous sequence of the Wolbachia organisms of O. volvulus. These data are, to our knowledge, the first to show that antibiotic therapy can be lethal to adult filariae. They suggest that tetracycline therapy is likely to be macrofilaricidal against O. volvulus infections in humans and, since similar Wolbachia organisms occur in a number of other filarial nematodes, against those infections too. In that the elimination of Wolbachia preceded the resolution of the filarial infections, they suggest that in O. ochengi at least, the Wolbachia organisms play an essential role in the biology and metabolism of the filarial worm. (+info)
(6/68) CD4(+) depletion selectively inhibits eosinophil recruitment to the cornea and abrogates Onchocerca volvulus keratitis (River blindness).
Previous studies demonstrated that in the murine model of Onchocerca volvulus keratitis, neutrophils and eosinophils are recruited into the cornea in a biphasic manner in response to intrastromal injection. To determine if CD4(+) T cells regulate migration of neutrophils and eosinophils into the cornea, CD4(+) cells were depleted using monoclonal antibody GK1.5 before intrastromal injection of parasite antigens. Depletion of CD4(+) cells abrogated corneal opacification at later but not early stages of disease. Consistent with this observation, CD4 depletion significantly impaired recruitment of eosinophils to the cornea but had no effect on neutrophils. These data indicate that CD4(+) T cells mediate sustained O. volvulus keratitis by regulating eosinophil recruitment to the cornea. (+info)
(7/68) Impaired eosinophil recruitment to the cornea in P-selectin-deficient mice in Onchocerca volvulus keratitis (River blindness).
PURPOSE: A murine model of helminth-induced keratitis (river blindness) that is characterized by a biphasic recruitment of neutrophils (days 1-3) and eosinophils (days 3+) to the cornea has been developed. The purpose of this study was to determine the relative contribution of P- and E-selectin in recruitment of these inflammatory cells from limbal vessels to the corneal stroma. METHODS: P- and E-selectin gene knockout (-/-) mice were immunized with antigens extracted from the parasitic helminth Onchocerca volvulus. One week after the last immunization, parasite antigens were injected directly into the corneal stroma. Mice were killed on days 1 and 3 postchallenge, and eyes were immunostained with either anti-eosinophil major basic protein (MBP) or with anti-neutrophil Ab. The number of cells in the cornea was determined by direct counting. RESULTS: Recruitment of eosinophils to the cornea was significantly impaired in P-selectin(-/-) mice (63.9% fewer eosinophils on day 1 [P: = 0.0015], and 61% fewer on day 3 [P: < 0.0001]) compared with control C57BL/6 mice. In contrast, P-selectin deficiency had no effect on neutrophil recruitment to the cornea. There was no inhibition of eosinophil and neutrophil migration to the corneas of E-selectin(-/-) mice, indicating that there is no direct role for this adhesion molecule in helminth-induced keratitis. CONCLUSIONS: The present study demonstrates that P-selectin is an important mediator of eosinophil recruitment to the cornea. P-selectin interactions may therefore be potential targets for immunotherapy in eosinophil-mediated ocular inflammation. (+info)
(8/68) CXC chemokine receptor 2 but not C-C chemokine receptor 1 expression is essential for neutrophil recruitment to the cornea in helminth-mediated keratitis (river blindness).
Infiltration of neutrophils and eosinophils into the mammalian cornea can result in loss of corneal clarity and severe visual impairment. To identify mediators of granulocyte recruitment to the corneal stroma, we determined the relative contribution of chemokine receptors CXC chemokine receptor (CXCR)-2 (IL-8R homologue) and CCR1 using a murine model of ocular onchocerciasis (river blindness) in which neutrophils and eosinophils migrate from peripheral vessels to the central cornea. CXCR2(-/-) and CCR1(-/-) mice were immunized s.c. and injected into the corneal stroma with Ags from the parasitic helminth Onchocerca volvulus. We found that production of macrophage-inflammatory protein (MIP)-2, KC, and MIP-1 alpha was localized to the corneal stroma, rather than to the epithelium, which was consistent with the location of neutrophils in the cornea. CCR1 deficiency did not inhibit neutrophil or eosinophil infiltration to the cornea or development of corneal opacification. In marked contrast, neutrophil recruitment to the corneas of CXCR2(-/-) mice was significantly impaired (p < 0.0001 compared with control, BALB/c mice) with only occasional neutrophils detected in the central cornea. Furthermore, CXCR2(-/-) mice developed only mild corneal opacification compared with BALB/c mice. These differences were not due to impaired KC and MIP-2 production in the corneal stroma of CXCR2(-/-) mice, which was similar to BALB/c mice. Furthermore, although MIP-1 alpha production was lower in CXCR2(-/-) mice than BALB/c mice, eosinophil recruitment to the cornea was not impaired. These observations demonstrate the critical role for CXCR2 expression in neutrophil infiltration to the cornea and may indicate a target for immune intervention in neutrophil-mediated corneal inflammation. (+info)