Antimicrobial activities of chemokines: not just a side-effect?

The large family of chemoattractant cytokines (chemokines) embraces multiple, in part unrelated functions that go well beyond chemotaxis. Undoubtedly, the control of immune cell migration (chemotaxis) is the single, unifying response mediated by all chemokines, which involves the sequential engagement of chemokine receptors on migrating target cells. However, numerous additional cellular responses are mediated by some (but not all) chemokines, including angiogenesis, tumor cell growth, T-cell co-stimulation, and control of HIV-1 infection. The recently described antimicrobial activity of several chemokines is of particular interest because antimicrobial peptides are thought to provide an essential first-line defense against invading microbes at the extremely large body surfaces of the skin, lungs, and gastrointestinal-urinary tract. Here we summarize the current knowledge about chemokines with antimicrobial activity and discuss their potential contribution to the control of bacterial infections that may take place at the earliest stage of antimicrobial immunity. In the case of homeostatic chemokines with antimicrobial function, such as CXCL14, we propose an immune surveillance function in healthy epithelial tissues characterized by low-level exposure to environmental microbes. Inflammatory chemokines, i.e., chemokines that are produced in tissue cells in response to microbial antigens (such as pathogen-associated molecular patterns) may be more important in orchestrating the cellular arm in antimicrobial immunity.

Early loss of arteriolar smooth muscle cells: more than just a pericyte loss in diabetic retinopathy

Incipient diabetic retinopathy is characterized by increased capillary permeability and progressive capillary occlusion. The earliest structural change is the loss of pericytes (PC) from the retinal capillaries. With the availability of the XLacZ mouse, which expresses the LacZ reporter in a PC/vascular smooth muscle cell (vSMC) specific fashion, we quantitatively assessed the temporal dynamics of smooth muscle cells in arterioles under hyperglycemic conditions. We induced stable hyperglycemia in XLacZ mice. After 4, 8, and 12 weeks of diabetes retinae were isolated and beta-galactosidase/lectin stained. The numbers of smooth muscle cells were counted in retinal whole mounts, and diameters of retinal radial and branching arterioles and venules were analyzed at different distances apart from the center of the retina. After eight weeks of diabetes, the numbers of vSMCs were significantly reduced in radial arterioles 1000 microm distant from the optic disc. At proximal sites of branching arterioles (400 microm distant from the center), and at distal sites (1000 microm), vSMC were significantly reduced already after 4 weeks (to a maximum of 31 %). These changes were not associated with any measurable variation in vessel diameters. These data indicate quantitatively that hyperglycemia not only causes pericyte loss, but also loss of vSMCs in the retinal vasculature. Our data suggest that arteriolar vSMC in the eye underlie similar regulations which induce early pericyte loss in the diabetic retina.

Understanding "Just Enough" Computer Users: Motivation Style and Proficiency

Among daily computer users who are proficient, some are flexible at accomplishing unfamiliar tasks on their own and others have difficulty. Software designers and evaluators involved with Human Computer Interaction (HCI) should account for any group of proficient daily users that are shown to stumble over unfamiliar tasks. We define "Just Enough" (JE) users as proficient daily computer users with predominantly extrinsic motivation style who know just enough to get what they want or need from the computer. We hypothesize that JE users have difficulty with unfamiliar computer tasks and skill transfer, whereas intrinsically motivated daily users accomplish unfamiliar tasks readily. Intrinsic motivation can be characterized by interest, enjoyment, and choice and extrinsic motivation is externally regulated. In our study we identified users by motivation style and then did ethnographic observations. Our results confirm that JE users do have difficulty accomplishing unfamiliar tasks on their own but had fewer problems with near skill transfer. In contrast, intrinsically motivated users had no trouble with unfamiliar tasks nor with near skill transfer. This supports our assertion that JE users know enough to get routine tasks done and can transfer that knowledge, but become unproductive when faced with unfamiliar tasks. This study combines quantitative and qualitative methods. We identified 66 daily users by motivation style using an inventory adapted from Deci and Ryan (Ryan and Deci 2000) and from Guay, Vallerand, and Blanchard (Guay et al. 2000). We used qualitative ethnographic methods with a think aloud protocol to observe nine extrinsic users and seven intrinsic users. Observation sessions had three customized phases where the researcher directed the participant to: 1) confirm the participant's proficiency; 2) test the participant accomplishing unfamiliar tasks; and 3) test transfer of existing skills to unfamiliar software.