Abdominal aortic aneurysm (AAA) is a prevalent life-threatening disease, where aortic wall degradation is mediated by accumulated immune cells. Although cytokines regulate inflammation within the aorta, their contribution to AAA via distant alterations, particularly in the control of hematopoietic stem cell (HSC) differentiation, remains poorly defined. Here we report a pathogenic role for the interleukin-27 receptor (IL-27R) in AAA, as genetic ablation of IL-27R protects mice from the disease development. Mitigation of AAA is associated with a blunted accumulation of myeloid cells in the aorta due to the attenuation of Angiotensin II (Ang II)-induced HSC expansion. IL-27R signaling is required to induce transcriptional programming to overcome HSC quiescence and increase differentiation and output of mature myeloid cells in response to stress stimuli to promote their accumulation in the diseased aorta. Overall, our studies illuminate how a prominent vascular disease can be distantly driven by a cytokine-dependent regulation of bone marrow precursors.

MicroRNAs play an important role in the regulation of many cellular processes. Undoubtedly, these regulatory molecules are involved in the pathogenesis of asthma, and therefore can be potential targets for treatment.

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The effect of naturally occurring cytokines on the chemiluminescence response of neutrophils from bronchoalveolar lavage and peripheral blood was studied in patients with chronic bronchitis. It was found that the response of neutrophils from bronchoalveolar lavage differs from that of peripheral blood neutrophils. The cytokines prestimulated the peripheral blood neutrophils for chemiluminescence. Key Words: cytokines; chemiluminescence; chronic bronchitisBronchoalveolar neutrophils and macrophages act as effector cells, hnpairments of the phagocytic component of ilnlnunity manifest themselves in reduced activity of alveolar macrophages, decrease in their content in bronchial mucus, increased content of functionally defective neutrophils, high activity of elastase and collagenase, and the presence of active oxygen forms in bronchoalveolar lavage [5,7]. The protective and damaging activities of puhnonary neutrophils have not been studied in sufficient detail. In the present study we used a model of spontaneous and stimulated chemiluminescence to deterlnine the role of cytokines in the regulation of functional activity of puhnonary and peripheral blood neutrophils in chronic nonspecific puhnonary diseases. Functional activity of neutrophils was assessed by measuring luminol-dependent chemiluminescence (LDCL) in an L1251 lmninometer (LKBWallac). Neutrophil suspension was prepared by incubating heparinized (20 U/lnl) venous blood (3 ml) with 3% gelatine solution at 37"C for 15 rain. The resultant cell suspension was twice washed with lnedium 199. Cellular composition was determined by the Zadorozhnyi-Dozlnorov staining. The neutrolghil count was adjusted to 2x106 cells/ml. Bronchoalveolar lavage was obtained by the conventional method. Cell suspension was prepared by filtration of the lavage through a capron filter and centrifugation in medimn 199 15 min at 400g and for 10 min at 200g. The viability and counts of neutrophils and macrophages were deterlnined using Zadorozhnyi-Dozmorov stain. The neutrophil content of the suspension was adjusted to 2x 106 cells/ml. Since the amplitude and the rate of neutrophilic CL response development are greater than those in macrophages [2], we neglected the contribution of lnacrophages to the chemilulninescence of the suspension. The chemiluminescence of other cells (lymphocytes and 0007-4888/98/0010-01035520,00 ~ Kluwer Academic/l)lemm~ |h,bti~h~w~ MATERIALS AND METHODS Neutrophils

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