Antimicrobial action of calprotectin that does not involve metal withholding.

Calprotectin is a potent antimicrobial that inhibits the growth of pathogens by tightly binding transition metals such as Mn and Zn, thereby preventing their uptake and utilization by invading microbes. At sites of infection, calprotectin is abundantly released from neutrophils, but calprotectin is also present in non-neutrophil cell types that may be relevant to infections. We show here that in patients infected with the Lyme disease pathogen Borreliella (Borrelia) burgdorferi, calprotectin is produced in neutrophil-free regions of the skin, in both epidermal keratinocytes and in immune cells infiltrating the dermis, including CD68 positive macrophages. In culture, B. burgdorferi's growth is inhibited by calprotectin, but surprisingly, the mechanism does not involve the classical withholding of metal nutrients. B. burgdorferi cells exposed to calprotectin cease growth with no reduction in intracellular Mn and no loss in activity of Mn enzymes including the SodA superoxide dismutase. Additionally, there is no obvious loss in intracellular Zn. Rather than metal depletion, we find that calprotectin inhibits B. burgdorferi growth through a mechanism that requires physical association of calprotectin with the bacteria. By comparison, calprotectin inhibited E. coli growth without physically interacting with the microbe, and calprotectin effectively depleted E. coli of intracellular Mn and Zn. Our studies with B. burgdorferi demonstrate that the antimicrobial capacity of calprotectin is complex and extends well beyond simple withholding of metal micronutrients.

Salivary levels of interleukin-8 and growth factors are modulated in patients with geographic tongue.

OBJECTIVES: The aim of the study was to determine the levels of salivary epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) as well as interleukin-8 (IL-8) in patients with geographic tongue (GT), as compared to control subjects. METHODOLOGY: An enzyme-linked immunosorbent assay was used to measure the levels of IL-8, EGF and VEGF in whole saliva samples collected from 34 patients with GT and 38 control subjects. The patients and controls were grouped and matched according to age, gender and the presence of systemic diseases, which are factors that may influence the levels of salivary biomarkers. RESULTS: All patients with GT displayed significantly higher levels of IL-8 than the controls (P < 0.001). The young female patients also showed reduced levels of EGF (P < 0.05) and VEGF (P < 0.05), as compared to the young male patients where no such differences were observed. Interestingly, high levels of IL-8 (P < 0.001) and VEGF (P < 0.05) were detected in the patients with GT who also suffered from hypertension. CONCLUSION: We consider IL-8 an inflammatory mediator, which contributes to the acute inflammatory response found in GT. EGF and VEGF also seem to be involved in the pathophysiology of GT.

T-Helper 17 Cell Cytokine Responses in Lyme Disease Correlate With Borrelia burgdorferi Antibodies During Early Infection and With Autoantibodies Late in the Illness in Patients With Antibiotic-Refractory Lyme Arthritis.

BACKGROUND: Control of Lyme disease is attributed predominantly to innate and adaptive T-helper 1 cell (TH1) immune responses, whereas the role of T-helper 17 cell (TH17) responses is less clear. Here we characterized these inflammatory responses in patients with erythema migrans (EM) or Lyme arthritis (LA) to elucidate their role early and late in the infection. METHODS: Levels of 21 cytokines and chemokines, representative of innate, TH1, and TH17 immune responses, were assessed by Luminex in acute and convalescent sera from 91 EM patients, in serum and synovial fluid from 141 LA patients, and in serum from 57 healthy subjects. Antibodies to Borrelia burgdorferi or autoantigens were measured by enzyme-linked immunosorbent assay. RESULTS: Compared with healthy subjects, EM patients had significantly higher levels of innate, TH1, and TH17-associated mediators (P ≤ .05) in serum. In these patients, the levels of inflammatory mediators, particularly TH17-associated cytokines, correlated directly with B. burgdorferi immunoglobulin G antibodies (P ≤ .02), suggesting a beneficial role for these responses in control of early infection. Late in the disease, in patients with LA, innate and TH1-associated mediators were often >10-fold higher in synovial fluid than serum. In contrast, the levels of TH17-associated mediators were more variable, but correlated strongly with autoantibodies to endothelial cell growth factor, matrix metalloproteinase 10, and apolipoprotein B-100 in joints of patients with antibiotic-refractory LA, implying a shift in TH17 responses toward an autoimmune phenotype. CONCLUSIONS: Patients with Lyme disease often develop pronounced TH17 immune responses that may help control early infection. However, late in the disease, excessive TH17 responses may be disadvantageous by contributing to autoimmune responses associated with antibiotic-refractory LA.

[Salivary glands and oral mucous membrane status in patients with chronic hepatitis].

The status of salivary glands and oral mucous membrane was investigated in 50 patients with chronic active hepatitis against the background of chronic alcoholism. The check up disclosed sialadenosis in 38% of patients and in 54% of patients - such diseases of oral mucous membrane as stomatitis, candidosis and geographic tonque. Besides there were disclosed such disturbances as big and small salivary glands secretion reduction, mixed saliva viscosity increase, increase of protein, P, K, Na and catalase content in it, glycogen hyperaccumulation in gingival tissues. The received data indicated the necessity of dispensary supervision of such patients and their treatment in stomatologist.

Expression of intermediate filaments in human tongue mucosa.

The specific inflammatory lesions of the human tongue, namely fissured tongue and geographic tongue, have been found to differ clinically and histologically from each other and from healthy appearing tongue (control). In this study we describe expression of cytokeratin, vimentin and desmin intermediate filaments in these tongue forms. The most important findings were seen in fissured tongue; strong positive staining of cytokeratin proteins indicate the incomplete keratinization of the epithelium, vimentin staining was irregular indicating subepithelial edema and desmin expression showed the destruction of the uppermost muscle cells. The corresponding changes of geographic tongue were similar but slight when compared with those of fissured tongue. Different immunohistochemical methods can supplement the information obtained from tongue biopsies by conventional methods and lead to a better understanding of the morphology of the tongue mucosa.

Electron microscopy of composite and intranuclear keratohyalin granules in geographic tongue of psoriasis.

Composite and intranuclear keratohyalin granules were observed in an electron-microscopic study of geographic tongue of psoriasis. The significance of intranuclear keratohyalin is not known, but it seems to be related to the disturbed proliferation and differentiation of keratinocytes in psoriasis.