The borough of Ocholo, on the western side of the Ethiopian Rift Valley, is an endemic focus for Leishmania aethiopica infection and has been surveyed thrice between 1987 and 1990. In 1989, 3022 inhabitants (> 95% of the population) were interviewed and examined. The overall prevalence of localized cutaneous leishmaniasis (LCL) was 3.6-4.0%, with a peak value of 8.5% in the 0-10 years old age group. In half of the patients the active disease was estimated to last for 9.6 +/- 6 months; in 10%, it exceeded 3 years. Scars of LCL were present in 34.3% of the residents. Leishmanin skin tests were positive in 54% of 120 school-children without signs of the disease. Therefore, in Ocholo a minimum of 71.6% of the population has been exposed to L. aethiopica infection. Two cases of the diffuse form of cutaneous leishmaniasis were observed. In this highland biotope, Phlebotomus pedifer was found to be the major, and possibly the only, vector for L. aethiopica.
To determine the relative in vivo importance of endothelial expressed adhesion molecules to eosinophil rolling, adhesion, and transmigration, we have induced eosinophilic peritonitis using ragweed allergen in P-selectin–deficient, intracellular adhesion molecule-1 (ICAM-1)–deficient and control wild-type mice. Circulating leukocytes visualized by intravital microscopy exhibited reduced rolling and firm adhesion in P-selectin–deficient mice and reduced firm adhesion in ICAM-1–deficient mice. Eosinophils exhibited reduced rolling and firm adhesion to endothelium in P-selectin–deficient mice. Eosinophil recruitment in P-selectin–deficient mice (∼75% inhibition of eosinophil recruitment) and ICAM-1–deficient mice (∼67% inhibition of eosinophil recruitment) was significantly reduced compared with wild-type mice. Eosinophil recruitment was not completely inhibited in P-selectin/ICAM-1 double-mutant mice (eosinophil recruitment inhibited ∼62%). However, pretreatment of P-selectin/ICAM-1–deficient mice with an anti-vascular cell adhesion molecule (VCAM) antibody induced near complete inhibition of eosinophil recruitment. Overall, these studies show that eosinophil rolling and firm adhesion is significantly reduced in P-selectin–deficient mice and that P-selectin, ICAM-1, and VCAM are important to eosinophil peritoneal recruitment after ragweed challenge.
Leishmania parasites invade host macrophages, causing infections that are either limited to skin or spread to internal organs. In this study, 3 species causing cutaneous leishmaniasis, L. major, L. aethiopica and L. tropica, were tested for their ability to interfere with apoptosis in host macrophages in 2 different lines of human monocyte-derived macrophages (cell lines THP-1 and U937) and the results confirmed in peripheral blood mononuclear cells (PBMC). All 3 species induced early apoptosis 48 h after infection (expression of phosphatidyl serine on the outer membrane). There were significant increases in the percentage of apoptotic cells both for U937 and PBMC following infection with each of the 3 species. Early apoptotic events were confirmed by mitochondrial membrane permeabilization detection and caspase activation 48 and 72 h after infection. Moreover, the percentage of infected THP-1 and U937 macrophages increased significantly (up to 100 %) following treatment with an apoptosis inducer. Since phosphatidyl serine externalization on apoptosing cells acts as a signal for engulfment by macrophages, induction of apoptosis in the parasitized cells could actively participate in spreading the infection. In summary, parasite-containing apoptotic bodies with intact membranes could be released and phagocytosed by uninfected macrophages.
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