Birdlike growth and mixed-age flocks in avimimids (Theropoda, Oviraptorosauria).

Avimimids were unusual, birdlike oviraptorosaurs from the Late Cretaceous of Asia. Initially enigmatic, new information has ameliorated the understanding of their anatomy, phylogenetic position, and behaviour. A monodominant bonebed from the Nemegt Formation of Mongolia showed that some avimimids were gregarious, but the site is unusual in the apparent absence of juveniles. Here, a second monodominant avimimid bonebed is described from the Iren Dabasu Formation of northern China. Elements recovered include numerous vertebrae and portions of the forelimbs and hindlimbs, representing a minimum of six individuals. Histological sampling of two tibiotarsi from the bonebed reveals rapid growth early in ontogeny followed by unexpectedly early onset of fusion and limited subsequent growth. This indicates that avimimids grew rapidly to adult size, like most extant birds but contrasting other small theropod dinosaurs. The combination of adults and juveniles in the Iren Dabasu bonebed assemblage provides evidence of mixed-age flocking in avimimids and the onset of fusion in young individuals suggests that some of the individuals in the Nemegt Formation bonebed may have been juveniles. Regardless, these individuals were likely functionally analogous to adults, and this probably facilitated mixed-age flocking by reducing ontogenetic niche shift in avimimids.

[Advances in the p75 neurotrophic factor receptor in stomatology].

The p75 neurotrophic factor receptor is a low affinity receptor for neurotrophic factors and plays an important role in nerve growth, development and function integrity. It is closely related to dental development, oral and maxillofacial tumor, nerve repair and tissue engineering. It shows good prospect for application. In this paper, the research progress of p75 neurotrophic factor receptor in Stomatology is reviewed.

[Joint effect of smoking and diabetes on stroke].

Objective: To explore the interaction of smoking and diabetes on stroke. Methods: In this case-control study, a face to face questionnaire survey was conducted. Logistic regression models were used to analyze the relationship between smoking or diabetes and stroke. The indicators of interaction were calculated according to the Bootstrap method in this study. Results: A total of 918 cases and 918 healthy controls, who participated in the chronic disease risk factor survey in Xuzhou in 2013, were included in this study. Logistic regression analysis found that cigarette smoking was associated with stroke (OR=1.63, 95%CI: 1.33-2.00), and diabetes was also associated with stroke (OR=2.75, 95%CI: 2.03-3.73) after adjusting confounders. Compared with those without diabetes and smoking habit, the odds ratio of stroke in those with diabetes and smoking habits was 8.94 (95%CI:3.77-21.19). Diabetes and smoking combined interaction index was 3.65 (95%CI: 1.68-7.94), the relative excess risk was 5.77 (95%CI: 0.49-11.04), the attributable proportion was 0.65 (95%CI: 0.42-0.87). Conclusion: The results suggest that there are additive interactions between smoking and diabetes on stroke.

[Trend analysis on the death rate of ischemic heart disease and cerebrovascular disease among Xuzhou residents from 2011 to 2015].

Objective: To analyze the epidemiological characteristics and trend of ischemic heart disease and cerebrovascular disease mortality among Xuzhou residents from 2011 to 2015. Methods: The mortality data of the ischemic heart disease and cerebrovascular disease were obtained from the registration disease surveillance system covering the residents of the city from 2011 to 2015. Ischemic heart disease and cerebrovascular disease were identified according to the international classification of diseases (ICD-10), Ischemic heart diseases include I20 to I25 (angina pectoris, acute myocardial infarction, certain current complications following acute myocardial infarction, other acute ischemic heart diseases chronic ischemic heart disease); cerebrovascular diseases include I60 to I69 (subarachnoid hemorrhage, intracerebral hemorrhage, other non-traumatic hemorrhage, cerebral infarction, stroke not specified as hemorrhage or infarction, other cerebrovascular diseases, sequelae of cerebrovascular disease). Results: (1)From 2011 to 2015, the chronic ischemia Cardio-Cerebrovascular disease mortality of residents in Xuzhou was 261.2 per one hundred thousand (129 950/49 748 321), 269.9 per one hundred thousand(69 562/25 775 930)for male residents, 252.0 per one hundred thousand(60 388/23 972 391)for female residents, the mortality rate in men was significantly higher than that in women (P<0.05). The chronic ischemic Cardio-Cerebrovascular disease mortality rate of urban residents was 243.8 per one hundred thousand(17 049/6 993 787), which was lower than the rate of rural residents (264.0 per one hundred thousand(112 901/42 754 534), P<0.05). (2)From 2011 to 2015, the mortality rate of ischemic heart disease in Xuzhou city remained unchanged: 117.1 per one hundred thousand(11 416/9 747 768), 126.8 per one hundred thousand(12 177/9 600 745), 112.0 per one hundred thousand(11 184/9 986 877), 115.2 per one hundred thousand(11 697/10 151 842), 117.1 per one hundred thousand(12 019/10 261 089, P>0.05). The mortality rate of cerebrovascular disease were 154.0 per one hundred thousand(15 014/9 747 768), 155.9 per one hundred thousand(14 964/9 600 745), 143.5 per one hundred thousand(14 330/9 986 877), 135.5 per one hundred thousand(13 752/10 151 842), 130.6 per one hundred thousand(13 397/10 261 089)respectively, presented with a downward trend(P<0.05). The mortality rate of ischemic cerebrovascular disease were 62.7 per one hundred thousand(6 108/9 747 768), 74.7 per one hundred thousand(7 176/9 600 745), 72.3 per one hundred thousand(7 221/9 986 877), 70.9 per one hundred thousand(7 200/10 151 842)and 72.4 per one hundred thousand(7 431/10 261 089)respectively(P>0.05). The mortality rate of hemorrhagic cerebrovascular disease were 77.6 per one hundred thousand(7 562/9 747 768), 71.6 per one hundred thousand(6 873/9 600 745), 61.2 per one hundred thousand(6 115/9 986 877), 55.3 per one hundred thousand(5 613/10 151 842)and 46.4 per one hundred thousand(4 763/10 261 089)respectively, presented with a downward trend(P<0.05). (3)The average death age due to ischemic heart diseases of all residents was (77.0±13.1)years old, (76.4±13.2) years old among urban residents, (77.1±7.1 )years old among rural residents, (74.3±13.5)years old for male residents, (80.0±12.0) years old for female residents. The average death age due to ischemic cerebrovascular diseases of all residents was (76.4±11.9)years old, (76.5±12.3) years old among urban residents, (76.4±11.9 )years old among rural residents, (74.3±12.2)years old among male residents, (79.0±11.1) years old among female residents. From 2011 to 2015, the death age due to ischemic heart diseases were (76.3±13.5), (77.2±13.0), (76.6±13.3), (77.1±12.9)and(77.8±12.9)years old respectively; the death age due to cerebrovascular disease were (75.8±12.1), (76.3±11.8), (76.6±11.8), (76.6±12.0)and(77.1±11.9)years old respectively. The Spearman rank correlation analysis showed that the death age due to ischemic heart disease and cerebrovascular disease increased year by year in the past 5 years. (r value was 0.033 and 0.038, respectively, all P<0.01). Conclusion: From 2011 to 2015, the mortality of hemorrhagic cerebrovascular disease decreased, while the mortality of ischemic cardiovascular and cerebrovascular diseases remained unchanged among Xuzhou residents.

Correlation among RKIP expression, NF-κB p65 levels, and T-lymphocyte subsets in gastric cardia adenocarcinoma.

The aim of this study was to characterize variations in Raf kinase inhibitor protein (RKIP) expression and related signaling molecules in gastric cardia adenocarcinoma. Cancerous and precancerous tissues were collected from patients with gastric cardia adenocarcinoma and normal tissue was collected from healthy controls. RKIP expression was detected in these tissues and the serum levels of NF-κB p65 and T-lymphocyte subsets were measured. Positive RKIP expression was higher in gastric cardia adenocarcinoma tissues than in precancerous tissues. The serum level of total NF-κB p65 was higher in patients with gastric cardia adenocarcinoma than in healthy controls. Levels of NF-κB p65 did not correlate with positive and negative expression of RKIP, but were higher in patients with lymph node metastasis than in those without it. The cellular immune function of the gastric cardia adenocarcinoma group was lower than in normal controls, particularly in cases with negative RKIP expression. RKIP is downregulated in gastric cardia adenocarcinoma tissues, which is related to the occurrence, progression, invasion, and metastasis of tumors. The possible mechanism for this may be the inhibition of NF-κB activity and cellular immune function, which allows for the escape of tumor cells from immune surveillance.

Interleukin-18 and IL18 -607A/C and -137G/C gene polymorphisms in patients with penicillin allergy.

This study investigated the association between polymorphisms (-607A/C and -137G/C) in the promoter region of the IL18 gene (which encodes interleukin [IL]-18) and serum levels of IL-18, using standard genotyping techniques (sequence specific primer-polymerase chain reaction) and an enzyme-linked immunosorbent assay, respectively, in patients allergic to penicillin. A higher frequency of A alleles and the AA genotype was found at position -607A/C in patients allergic to penicillin than in control subjects. For the -137G/C position, the C allele was more frequent in patients allergic to penicillin than in control subjects. Haplotype analysis showed that the -607A/-137C haplotype was more frequent in patients allergic to penicillin than in control subjects. The patients had a significantly higher serum IL-18 level than the control subjects. In conclusion, IL18 -607A/C and -137G/C promoter polymorphisms are associated with susceptibility to penicillin allergy. In particular, the -137G/C position appears to play an important role in IL18 expression.

Expression of coxsackie and adenovirus receptor distinguishes transitional cancer states in therapy-induced cellular senescence.

Therapy-induced cellular senescence describes the phenomenon of cell cycle arrest that can be invoked in cancer cells in response to chemotherapy. Sustained proliferative arrest is often overcome as a contingent of senescent tumor cells can bypass this cell cycle restriction. The mechanism regulating cell cycle re-entry of senescent cancer cells remains poorly understood. This is the first report of the isolation and characterization of two distinct transitional states in chemotherapy-induced senescent cells that share indistinguishable morphological senescence phenotypes and are functionally classified by their ability to escape cell cycle arrest. It has been observed that cell surface expression of coxsackie and adenovirus receptor (CAR) is downregulated in cancer cells treated with chemotherapy. We show the novel use of surface CAR expression and adenoviral transduction to differentiate senescent states and also show in vivo evidence of CAR downregulation in colorectal cancer patients treated with neoadjuvant chemoradiation. This study suggests that CAR is a candidate biomarker for senescence response to antitumor therapy, and CAR expression can be used to distinguish transitional states in early senescence to study fundamental regulatory events in therapy-induced senescence.

Difference in expression level and localization of DNA polymerase beta among human esophageal cancer focus, adjacent and corresponding normal tissues.

The aim of this paper was to study the expression level and localization of DNA polymerase beta (polbeta) and the difference in those among the human esophageal cancer focus, cancer adjacent and corresponding normal esophageal tissues. These three kinds of tissues were collected from surgically resected tissues in 17 patients with esophageal carcinoma in Linzhou, China. Each of a total of 51 tissue pieces was divided into two aliquots: one aliquot for detection of polbeta expression by in situ hybridization and by immunohistochemistry; another for detection of polbeta expression by RNA dot blot and immunoblotting. In the tissue specimens detected by in situ hybridization and immunohistochemistry, the cancer focus tissue had much stronger polbeta expression signals localized in the scattered heteromorphologic cancer cells. The cancer adjacent tissue exhibited slightly stronger polbeta signals mainly localized in the epithelial proliferating cells and the corresponding normal tissue displayed weak polbeta signals basically located in the epithelial basal cells. The difference in expression level of polbeta among the three kinds of tissues detected by RNA dot blot and immunoblotting was similar to the above results. Further, the truncated POLB could be demonstrated in both cancer focus and cancer adjacent tissues, but could not be found in the corresponding normal tissue in immunoblotting. The results suggest that the overexpression of polbeta with truncated form may be a potential biomarker for early diagnosis of human esophageal carcinoma.

Relationships between skin test, specific IgE and levels of cytokines in patients with penicillin allergy.

The aim of this study was to investigate the relationships between skin test, specific immunoglobulin (Ig) E and cytokines in penicillin allergy. We collected the sera of 259 patients with historical positive skin test to penicillins, with immediate positive skin test and with a negative skin test results. The positive rate of specific IgE antibodies in 259 patients was 62.2% (161) by using radioallergosorbent test (RAST). Of the eight kinds of antigenic determinants, the positive rates of specific IgE to major and minor determinants were 43.63% (113) and 52.51% (136), respectively (p < 0.05). In 122 patients with immediate positive skin test, when the degrees of skin test were +, 2+, 3+ and 4+, the positive rates of specific IgE were 45.7, 57.1, 85.2 and 100%, respectively. The levels of interleukin (IL)-4, IL-13 and interferon (IFN)-gamma in the sera of patients with positive skin test were significantly increased with the degree of positive skin test (p < 0.05). The combined use of major and minor determinants in RAST offers the better test for the detection of penicillin-specific IgE antibodies. IL-4, IL-13 and IFN-gamma play important roles in penicillin allergy.

Prominent role of P-selectin in the development of advanced atherosclerosis in ApoE-deficient mice.

BACKGROUND: Adhesive interactions between leukocytes and endothelial cells are characteristic of the development of atherosclerotic lesions, but the receptors involved remain to be defined. P-selectin is an adhesion receptor expressed on activated endothelial cells or platelets and was shown to be involved in fatty streak formation in LDL receptor-deficient mice on an atherogenic diet. The main purpose of this study is to examine the role of P-selectin in the spontaneous development of advanced atherosclerosis in apoE-deficient mice. METHODDS AND RESULTS: We intercrossed P-selectin-deficient mice with mice lacking apoE and compared lesion development in apoE-deficient mice with P-selectin (apoE(-/-) P(+/+)) and without P-selectin (apoE(-/-) P(-/-)) that were fed normal mouse chow. At 4 months of age, apoE(-/-) P(-/-) mice had 3. 5-fold smaller aortic sinus lesions than apoE(-/-) P(+/+) mice. These were limited to fatty streaks in the apoE(-/-) P(-/-) mice, whereas 70% of apoE(-/-) P(+/+) lesions contained smooth muscle cells. Significantly more of the aortic sinus circumference was covered by lesions in the apoE(-/-) P(+/+) animals. The P-selectin genotype affected macrophage recruitment, because twice as many mononuclear cells were present in the P-selectin-positive lesions. At 15 months, the lesions progressed to the fibrous plaque stage in both genotypes and spread throughout the aorta, but this process was delayed in apoE(-/-) P(-/-) mice. In the aortic sinus, the lesions of the apoE(-/-) P(-/-) mice were 2.6-fold smaller and less calcified. CONCLUSIONS: P-selectin appears to be a key adhesion receptor mediating leukocyte recruitment into lesions and promoting advanced atherosclerosis in apoE-deficient mice.

Donor MHC and adhesion molecules in transplant arteriosclerosis.

Transplant-associated arteriosclerosis remains an obstacle to long-term graft survival. To determine the contribution to transplant arteriosclerosis of MHC and adhesion molecules from cells of the donor vasculature, we allografted carotid artery loops from six mutant mouse strains into immunocompetent CBA/CaJ recipients. The donor mice were deficient in either MHC I molecules or MHC II molecules, both MHC I and MHC II molecules, the adhesion molecule P-selectin, intercellular adhesion molecule (ICAM)-1, or both P-selectin and ICAM-1. Donor arteries in which ICAM-1, MHC II, or both MHC I and MHC II were absent showed reductions in neointima formation of 52%, 33%, and 38%, respectively, due primarily to a reduction in smooth muscle cell (SMC) accumulation. In P-selectin-deficient donor arteries, neointima formation did not differ from that in controls. In donor arteries lacking both P-selectin and ICAM-1, the size of the neointima was similar to that in those lacking ICAM-1 alone. In contrast, neointima formation increased by 52% in MHC I-deficient donor arteries. The number of CD4-positive T cells increased by 2.8-fold in MHC I-deficient arteries, and that of alpha-actin-positive SMCs by twofold. These observations indicate that ICAM-1 and MHC II molecules expressed in the donor vessel wall may promote transplant-associated arteriosclerosis. MHC I molecules expressed in the donor may have a protective effect.

Mechanisms for induction of L-selectin loss from T lymphocytes by a cryptococcal polysaccharide, glucuronoxylomannan.

Disseminated cryptococcosis is accompanied by cryptococcal polysaccharides in the serum and the lack of cellular infiltrates in infected tissues. Cryptococcal polysaccharides given intravenously to mice inhibit the influx of T lymphocytes into the sites of cell-mediated immune response. The focus here was to determine whether cryptococcal polysaccharides modulate the expression of molecules, such as L-selectin, that are important in extravasation of T cells. Cryptococcal glucuronoxylomannan (GXM), but not galactoxylomannan or mannoprotein, was found to cause loss of L-selectin from freshly isolated human T cells of both CD4 and CD8 subsets and from Jurkat cells. With the signaling-pathway inhibitors staurosporine (which inhibits protein kinase C) and herbimycin A (which inhibits protein tyrosine kinases), we showed that GXM or the cryptococcal culture filtrate antigen CneF directly induces L-selectin loss from CD4(+) and CD8(+) T cells via a herbimycin A-sensitive pathway(s) presumably involving one or more protein tyrosine kinases but not via a pathway involving protein kinase C. Loss of L-selectin from the T cells before the T cells have a chance to bind to L-selectin ligands on endothelial cells would be expected to prevent T-cell migration into inflamed tissues and/or lymph organs.

Leukocyte-endothelium adhesion molecules in atherosclerosis.

The genetic manipulation of mice has provided an invaluable tool for studying the molecular mechanism(s) involved in atherosclerotic lesion development and maturation. The use of these new animal models has demonstrated that leukocyte-endothelium adhesion receptors play a significant part in promoting monocyte recruitment and consequently lesion growth. The next phase of investigation should test whether the inhibition of these adhesion receptors can reproduce the powerful anti-atherosclerotic effects seen in the adhesion receptor-deficient mice.

The combined role of P- and E-selectins in atherosclerosis.

P- and E-selectins are adhesion molecules mediating the first step in leukocyte extravasation. Because their function in leukocyte adhesion is overlapping, we hypothesized that there might be a combined effect of these selectins on the development of atherosclerotic lesions. We bred P- and E-selectin-double-deficient mice onto the low-density lipoprotein receptor (LDLR)-deficient background (LDLR-/- P/E-/-) and compared lesion development in these mice to that in mice wild type for both selectins (LDLR-/- P/E+/+). After 8 wk on atherogenic diet, the LDLR-/- P/E-/- mice developed fatty streaks in the aortic sinus that were five times smaller than those in LDLR-/- P/E+/+ mice. The density of macrophages in the fatty streaks was comparable between LDLR-/- P/E+/+ and LDLR-/- P/E-/- mice. After 22 wk on the diet, the lesions spread throughout the aorta but this process was delayed in LDLR-/- P/E-/- mice. At 37 wk on diet, the lesions progressed to the fibrous plaque stage in both genotypes. However, the lesions in the aortic sinus in LDLR-/- P/E-/- mice were 40% smaller and less calcified than those of LDLR-/- P/E +/+ mice. Our results suggest that P- and E-selectins together play an important role in both early and advanced stages of atherosclerotic lesion development.

A new class of obesity genes encodes leukocyte adhesion receptors.

Obesity is a complex disease, and multiple genes contribute to the trait. The description of five genes (ob, db, tub, Ay, and fat) responsible for distinct syndromes of spontaneous monogenic obesity in mice has advanced our knowledge of the genetics of obesity. However, many other genes involved in the expression of this disease remain to be determined. We report here the identification of an additional class of genes involved in the regulation of adipose tissue mass. These genes encode receptors mediating leukocyte adhesion. Mice deficient in intercellular adhesion molecule-1 became spontaneously obese in old age on normal mouse chow or at a young age when provided with a diet rich in fat. Mice deficient in the counterreceptor for intercellular adhesion molecule-1, the leukocyte integrin alphaMbeta2 (Mac-1), showed a similar obesity phenotype. Since all mice consumed approximately the same amount of food as controls, the leukocyte function appears to be in regulating lipid metabolism and/or energy expenditure. Our results indicate that (i) leukocytes play a role in preventing excess body fat deposition and (ii) defects in leukocyte adhesion receptors can result in obesity.

Absence of P-selectin delays fatty streak formation in mice.

P-selectin is expressed on activated endothelium and platelets where it can bind monocytes, neutrophils, stimulated T cells, and platelets. Because recruitment of these cells is critical for atherosclerotic lesion development, we examined whether P-selectin might play a role in atherosclerosis. We intercrossed P-selectin-deficient mice with mice lacking the low density lipoprotein receptor (LDLR) because these mice readily develop atherosclerotic lesions on diets rich in saturated fat and cholesterol. The atherogenic diet stimulated leukocyte rolling in the mesenteric venules of LDLR-deficient mice, and the increase in adhesiveness of the vessels was P-selectin-dependent. Most likely due to the reduced leukocyte interaction with the vessel wall, P-selectin-deficient mice on diet for 8-20 wk formed significantly smaller fatty streaks in the cusp region of the aortae than did P-selectin-positive mice. This difference was more prominent in males. At 37 wk on diet, the lesions in the LDLR-deficient animals progressed to the fibrous plaque stage and were distributed throughout the entire aorta; their size or distribution was no longer dependent on P-selectin. Our results show that P-selectin-mediated adhesion is an important factor in the development of early atherosclerotic lesions, and that adhesion molecules such as P-selectin are involved in the complex process of atherosclerosis.

Cryptococcal polysaccharides bind to CD18 on human neutrophils.

CD18, the beta chain of the beta 2 integrin family of adhesion molecules, is associated with three different alpha chains (CD11a, -b, and -c) and is expressed on the surface of all types of leukocytes. CD18-containing molecules are up-regulated on the surface of neutrophils (polymorphonuclear cells [PMN]) in response to chemotactic agents and are implicated in mediating adhesion to an inflamed endothelium, which is a prerequisite to migration of PMN into infected tissues. In a previous study, we found that a cryptococcal culture filtrate (CneF), when injected into the bloodstream of mice to simulate the antigenemia in cryptococcosis, inhibits PMN accumulation at the site of an inflammatory stimulus. In the present study, we assessed the ability of CneF and its individual components, i.e., glucuronoxylomannan (GXM), galactoxylomannan (GalXM), and mannoprotein (MP), to interact with CD18 on human PMN. CneF labeled with 14C was shown to bind to human PMN in a dose-dependent manner. Pretreatment of PMN with anti-CD18, but not an isotype-matched control monoclonal antibody (MAb) or anti-CD11a MAb, blocked the binding of 14C-labeled CneF to PMN. In addition, CneF, GXM, and GalXM but not MP significantly blocked the binding of the anti-CD18 MAb to CD18 on the surface of unactivated and formyl methionyl leucyl phenylalanine-activated PMN as determined by indirect immunofluorescence staining and flow cytometric analysis. In the same experiments, the cryptococcal polysaccharides did not affect the binding of an anti-CD11a or anti-L-selectin MAb to the surface of PMN at 4 degrees C. The results suggest that CneF and its components GXM and GalXM bind to CD18 on human PMN. Based on our findings, we propose that CD18 is a possible molecular target of cryptococcal polysaccharides and that binding of the polysaccharides to CD18 has the potential to inhibit leukocyte infiltration into inflammatory sites.

The simultaneous measurement of low rates of CO2 and O2 exchange in biological systems.

An instrument for measuring low rates of biological O2 exchange using an open-flow gas analysis system is described. A novel differential O2 sensor that is capable of measuring as little as 0.4 Pa O2 against a back-ground of ambient air (20,900 Pa O2), yet has a dynamic range of +/- 2000 Pa O2 (i.e., +/- ca. 2% O2) is described. Baseline drift was typically less than 0.025 Pa min-1. The differential O2 sensor was incorporated into a respiratory quotient/photosynthetic quotient analyzer that contained other environmental sensors for atmospheric pressure, absolute O2 and CO2 concentration, temperature of the differential O2 sensor block, and differential pressure between reference and sample streams. Protocols for how these sensors can be used to calibrate the differential O2 sensor and to improve its stability with time are described. Together, the differential O2 sensor, the environmental sensors, and the simple calibration techniques allow for simultaneous, noninvasive, and accurate measurements of O2 and CO2 exchange in tissues with metabolic rates as low as about 0.1 mumol O2 or CO2 h-1. Example data are provided in which O2 differentials of 3 to 41 Pa O2 were measured in an open-flow system.

Cryptococcal polysaccharides induce L-selectin shedding and tumor necrosis factor receptor loss from the surface of human neutrophils.

High titers of cryptococcal polysaccharides in the serum and spinal fluid and the lack of cellular infiltrates in the infected tissues are hallmarks of disseminated cryptococcosis. Cryptococcal polysaccharides given intravenously to mice inhibit the influx of leukocytes into sites injected with inflammatory mediators. The purpose of this investigation was to determine if cryptococcal polysaccharides, i.e., glucuronoxylomannan (GXM), galactoxylomannan, and mannoprotein, affect expression of molecules on the surface of neutrophils that are important in extravasation. GXM in the absence of serum was shown to induce human neurophils to shed L-selectin, a molecule needed in the first step of neutrophil movement into tissues. In the presence of serum, GXM caused a further shedding of L-selectin. Shedding of L-selectin was evident by reduced amounts of L-selectin on the neutrophils treated with GXM and by increased levels of soluble L-selectin in the GXM-treated neutrophil supernatants. GXM also stimulated neutrophils to have reduced expression of TNF receptor. In contrast, GXM-treated neutrophils showed increased levels of CD15 and CD11b, and unchanged CD16 expression. In the absence of serum, galactoxylomannan and mannoprotein did not affect L-selectin, TNF receptor, CD15, CD11b, or CD16 on neutrophils but did induce loss of L-selectin in the presence of serum. Our results indicate that cryptococcal polysaccharides, especially GXM, can cause shedding of L-selectin from the surface of neutrophils, and this may prevent neutrophils from attaching to the endothelial cell surfaces. Blockage of this early step in cell migration from the vessels into tissues may be responsible in part for reduced cellular infiltration into infected tissues of individuals with disseminated cryptococcosis.