LL-37, derived from human cathelicidin, stimulates immune responses in neutrophils. Although FPR2 and P2X7 were proposed as LL-37 receptors, we have shown that among 21 neutrophil receptors only CXCR2 was down-regulated by LL-37. LL-37 functions similarly to CXCR2-specific chemokines CXCL1 and CXCL7 in terms of receptor down-regulation and intracellular calcium mobilization on freshly isolated neutrophils. Neutrophils pretreated with CXCL8, a chemokine that binds both CXCR1/2, completely blocked the calcium mobilization in response to LL-37, while LL-37 also partially inhibited ), further confirming the specificity of LL-37 for CXCR2 and not FPR2. Among all ligands tested (ATP, BzATP, WKYMVm, CXCL1, and LL-37), only LL-37 stimulated migration of monocytes (CXCR2 1 and FPR2 1) and migration was inhibited by the CXCR2 inhibitor SB225002. Moreover, CXCR2 but not CXCR1 was internalized in LL-37-treated neutrophils. Thus, our data provide evidence that LL-37 may act as a functional ligand for CXCR2 on human neutrophils.Key words: CXCR2 . LL-37 . Neutrophils . Receptor Supporting Information available online IntroductionHuman CAP-18, the only human cathelicidin identified in neutrophils [1], was later shown to be expressed in epithelial cells [2] and monocytes [3]. Cathelicidins are a family of antimicrobial peptides that are characterized by a conserved N-terminal cathelin domain and a variable C-terminal antimicrobial domain. This C-terminal domain is cleaved from the precursor by proteinase-3, releasing the $4.5 kD active a-helical peptide LL-37 [4]. Human CAP-18 has been shown to inhibit LPS and other bacterial components (lipoteichoic acid and noncapped lipoarabinomannan) that induce a variety of cellular responses, including release of TNF-a, nitric oxide, and tissue factor [5,6]. Other studies have revealed that LL-37 itself is a multifunctional modulator of innate immune responses. For example, LL-37 promotes wound neovascularization [7], re-epithelialization of healing skin [8], migration of human peripheral monocytes, neutrophils, CD41T cells, and mast cells Eur. J. Immunol. 2009. 39: 3181-3194 DOI 10.1002 Innate immunity 3181 [3,9,10], and stimulates the expression of over 40 genes by macrophages, including chemokines, such as CXCL8 , and their receptors, such as CXCR2 [6]. These data suggest that it is important to identify the specific receptors on cell surfaces responsible for LL-37 function. Initially, LL-37 was proposed to act through FPRL1 (newly named FPR2) to cause migration of monocytes with a general FPR2-like activity for neutrophil and T-lymphocyte migration [9], but subsequent studies challenged FPR2 as the receptor on epithelial cells, keratinocytes, and neutrophils [11][12][13]. Later, the ATP receptor P2X7 was proposed as the LL-37 receptor on monocytes [14]; however, it was unclear if LL-37 activated P2X7 through a direct or indirect mechanism. In our studies on the induction of neutrophil secondary necrosis on annexin V positive neutrophils [15], we found that among 21 cell surface recept...
We examined the association among anxiety, religiosity, meaning of life and mental health in a nonclinical sample from a Chinese society. Four hundred fifty-one Taiwanese adults (150 males and 300 females) ranging in age from 17 to 73 years (M = 28.9, SD = 11.53) completed measures of Beck Anxiety Inventory, Medical Outcomes Study Health Survey, Perceived Stress Scale, Social Support Scale, and Personal Religiosity Scale (measuring religiosity and meaning of life). Meaning of life has a significant negative correlation with anxiety and a significant positive correlation with mental health and religiosity; however, religiosity does not correlate significantly anxiety and mental health after controlling for demographic measures, social support and physical health. Anxiety explains unique variance in mental health above meaning of life. Meaning of life was found to partially mediate the relationship between anxiety and mental health. These findings suggest that benefits of meaning of life for mental health can be at least partially accounted for by the effects of underlying anxiety.
Objective: Minority families experience disparities in the diagnosis and management of autism spectrum disorder (hereafter "autism"). To date, the experiences of Chinese immigrant families in the United States have not been explored. Utilizing parent and provider perspectives, this research sought to identify barriers and facilitators to the diagnosis and management of autism among Chinese immigrant children. Methods:We conducted semi-structured qualitative interviews with sixteen parents of Chinese children diagnosed with autism and sixteen providers who assist in the diagnosis and management of autism. Participant characteristics were analyzed utilizing descriptive statistics. Interviews were audio-recorded, transcribed, translated, and independently coded by two researchers until consensus was reached. Coded data were analyzed using a modified grounded therapy approach.Results: Parents and providers both identified cultural beliefs as an influence on the understanding and acceptance of autism as a diagnosis. There was a high degree of alignment in themes related to barriers to health care access and parent-provider communication. Recommendations to improve the system of care include: (1) supporting communication, (2) cultural sensitivity, and (3) care coordination programming.Conclusions: Findings reinforce that diagnosis and treatment of autism should take into account culturally specific beliefs about child developmental norms, and address systems-, provider-, and family-level barriers.
The hepatitis C virus (HCV) infects more than 200 million people globally, with increasing incidence, especially in developing countries. HCV infection frequently progresses to chronic liver disease, creating a heavy economic burden on resourcepoor countries and lowering patient quality of life. Effective HCV diagnosis, treatment selection, and treatment monitoring are important in stopping disease progression. Serological assays, which detect anti-HCV antibodies in the patient after seroconversion, are used for initial HCV diagnosis. Qualitative and quantitative molecular assays are used to confirm initial diagnosis, determine viral load, and genotype the dominant strain. Viral load and genotype information are used to guide appropriate treatment. Various other biomarker assays are performed to assess liver function and enable disease staging. Most of these diagnostic methods are mature and routinely used in high-resource countries with well-developed laboratory infrastructure. Few technologies, however, are available that address the needs of low-resource areas with high HCV prevalence, such as Africa and Southeast Asia.
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