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IntroductionTrafficking of leukocytes is largely governed by interaction between adhesion molecules expressed on leukocytes and on the vascular endothelium of postcapillary venules. Selectins mediate the initial rolling and tethering events 1,2 following which integrins mediate firm adhesion 3 that in turn allows for transmigration of cells into the tissue. This cascade of adhesive interactions occurring between leukocytes and endothelial cells in postcapillary venules is well documented in the systemic microcirculation of many organs. 4,5 In the lungs, leukocyte transmigration is believed to occur primarily in alveolar capillaries. 6,7 Margination of neutrophils in pulmonary capillaries is largely independent of selectins and the CD18 integrins, 8,9 although neutrophil margination in response to formyl methionyl leucyl phenylalanine 10 and their prolonged sequestration in response to other mediators is L-selectindependent. [11][12][13] Marginated neutrophil numbers in the pulmonary circulation remain unchanged in E-, P-, or L-selectin genedisrupted mice. 11,14 The smaller diameter of the pulmonary capillaries allows close contact between neutrophils and capillary endothelium. Neutrophils have to deform and elongate in order to pass through the capillary segments, which possibly accounts for their delayed transit time through the pulmonary vasculature. 15 Recirculation and homing of naive T cells to peripheral lymph nodes requires L-selectin, 16 lymphocyte function-associated antigen-1 (LFA-1), 17 and CCL19/CCR7 interactions. 18 However, the mechanism(s) of lymphocyte trafficking to the lungs is not fully understood. In a murine model of pulmonary inflammation, intercellular adhesion molecule 1 (ICAM-1) has been implicated in lymphocyte recruitment to the lungs. 19 ␣ 4 integrin and its receptor VCAM-1 have been shown to play an important role in lymphocyte migration to the lungs following intratracheal challenge with sheep red blood cells, which causes a rapid induction of endothelial VCAM-1. 20,21 L-selectin and, to a larger extent, ICAM-1 have been shown to be important in lymphocyte migration to the lungs during an allergic inflammatory response in a mouse model of asthma. 22 In an adoptive transfer model for alloreactive CD4 T cells, adherence of T cells in the lungs was shown to be partially dependent on LFA-1 and its receptor ICAM-1. 23 Bacterial or viral infection has been shown to generate effector and memory CD8 T cells that marginate into nonlymphoid tissues, including the lungs, which suggests that these cells either continuously recirculate through peripheral tissues or reside in them permanently. 24 However, the homing mechanisms of cytotoxic CD8 T cells into the lungs have not been investigated so far.Cytotoxic T cells play a central role in the pathophysiology of many inflammatory lung diseases, wherein they accumulate in the alveolar space and/or in the interstitium 25,26 and function primarily in the clearance of virus infection. 27 We have previously described transgenic Balb/c mice expressing ...

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Angiodysplasias are a major cause of lower gastrointestinal bleeding in patients over the age of 60 years. Although multiple treatment modalities, both medical and surgical, are being used, there is no effective treatment option currently available. Our study defines the use of a novel drug that might be effective against bleeding from vascular malformations. Three patients with a diagnosis of angiodysplasia, who were transfusion dependent, were placed on the study drug. The need for blood transfusions was recorded over the study period and for 6 months after the end of the study. We saw a decreased need for transfusions within 12 weeks of starting the treatment in two patients, and they continued to remain free of transfusion requirement during the immediate follow-up period. The study drug was well tolerated. Thalidomide, with its antiangiogenic mechanism of action, seems to be a promising drug in bleeding angiodysplasias as a treatment option for patients unable to benefit from other available modalities of treatment.