A role for CXC chemokine receptor-2 in the pathogenesis of urogenital Chlamydia muridarum infection in mice.

We tested the hypothesis that a specific chemokine receptor, CXC chemokine receptor-2 (CXCR2), mediates acute inflammatory damage during chlamydial urogenital infection, which ultimately leads to the chronic sequelae of hydrosalpinx - a surrogate marker of infertility. Homozygous CXCR2 genetic knockouts (CXCR2-/-), heterozygous littermates (CXCR2+/-) or homozygous wild-type (wt) controls (CXCR2+/+) were infected intravaginally with Chlamydia muridarum. Although no change was observed in the infection in the lower genital tract based on CXCR zygosity, a delay in the ascension of infection into the upper genital tract was seen in CXCR2-/- mice. Significantly elevated peripheral blood neutrophil counts were observed in CXCR2-/- mice when compared with controls. Reduced rates of acute inflammatory indices were observed in the affected tissue, indicating reduced neutrophil extravasation capacity in the absence of CXCR2. Of note was a reduction in the postinfection development of hydrosalpinx that correlated with CXCR2 zygosity, with both CXCR2-/- (13%) and their CXCR2+/- (35%) littermates displaying significantly lower rates of hydrosalpinx formation than the wt CXCR2-sufficient mice (93%). We conclude that CXCR2 ligands are a major chemotactic signal that induces damaging acute inflammation and the resulting chronic pathology during the repair phase of the host response, but are dispensable for the resolution of infection.

A role for matrix metalloproteinase-9 in pathogenesis of urogenital Chlamydia muridarum infection in mice.

Matrix metalloproteinases (MMPs) are a family of host-derived enzymes involved in the turnover of extracellular matrix (ECM) molecules and the processing of cytokines, chemokines and growth factors. We have previously reported that global inhibition of MMP in Chlamydia muridarum urogenital tract infection of susceptible strains of female mice impeded ascension of C. muridarum into the upper genital tract, blunted acute inflammatory responses and reduced the rate of formation of chronic disease. Because we have also observed that MMP-9 (also known as gelatinase B) is expressed in relatively large quantities in susceptible strains of mice in response to infection during acute phases of infection, we explored this further in a more selected fashion. We infected MMP-9 gene knockout mice and wild type controls intravaginally with C. muridarum. Both groups of mice had similar isolation rates from the lower urogenital tract but the absence of MMP-9 resulted in a slightly lower isolation rate in the upper genital tract, blunted acute inflammatory indices in the affected tissues and a reduced rate of formation of hydrosalpinx-a surrogate marker of infertility. These results imply that MMP-9 is involved in pathogenesis of chlamydial infection in this model possibly by amplifying inflammatory responses.

Common house spiders are not likely vectors of community-acquired methicillin-resistant Staphylococcus aureus infections.

There is an increasing incidence in the number of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections in the United States. Skin and soft tissue infections caused by MRSA are often perceived as being preceded by a spider bite. Several possibilities exist to explain this phenomenon, including 1) spiders introduce MRSA into the bite wound and thereby serve as a potential vehicle or vector for MRSA; 2) MRSA colonization is an event secondary to the spider bite; and 3) the spider bite is a misguided way for patients or their physicians to explain the initial lesion of their skin or soft tissue infection. We hypothesized that if spiders were able to serve as vehicles or vectors for MRSA infections, they would be colonized with this pathogen. To test this hypothesis, we captured common household spiders and determined the patterns of normal microbial flora isolated from them. Spiders were collected from several homes by their occupants, photographed for identification, and cultured for external and internal microbial flora. Of > 100 spiders collected, none was found to carry Staphylococcus aureus or MRSA. Relatively low numbers of microbial flora were isolated, and only a single isolate with pathogenic potential in humans (Aeromonas spp.) was isolated. Common house spiders are unlikely to be a source of MRSA.

Inhibition of matrix metalloproteinases protects mice from ascending infection and chronic disease manifestations resulting from urogenital Chlamydia muridarum infection.

Matrix metalloproteinases (MMP) are a family of host-derived enzymes involved in the turnover of extracellular matrix molecules. We have previously reported enhanced expression of matrix metalloproteinases in Chlamydia muridarum urogenital tract infection of female mice. Kinetics and patterns of MMP expression as well as enhanced expression in susceptible strains of mice in the prior study implied a role for MMP in pathogenesis. To explore this further, we infected a susceptible strain of mice (C3H/HeN) with C. muridarum and treated two groups of mice with either one of two chemical inhibitors of MMP (MMPi; captopril and a chemically modified tetracycline) and reserved infected sham-treated mice as controls. Neither of the treatments affected shedding of viable chlamydiae from the lower urogenital tract, but the administration of either MMPi protected mice from the formation of hydrosalpinx-a surrogate marker of oviduct occlusion and infertility. Interestingly, the mechanism of protection for mice treated with chemically modified tetracycline 3, appeared to be related to prevention of ascending upper genital tract infection. These results imply that MMP are involved in pathogenesis of chlamydial infection in this model by mediating ascension of the infection into the upper genital tract.

Malignant breast tumor phospholipid profiles using (31)P magnetic resonance.

Biochemical markers improve the classification and staging of breast cancer and may refine management decisions if it can be shown that they correlate with accepted prognostic factors or patient outcome. Using phosphorus-31 magnetic resonance spectroscopy ((31)P MRS), we determined the phospholipid content of 43 malignant breast tumors, correlating the profiles with specific histopathologic and clinical features and hormone receptor status. Among the 14 phospholipids identified, the mean mole percentage of sphingomyelin, phosphatidylcholine, phosphatidylserine, phosphatidic acid, phosphatidylglycerol, and alkylacylphosphatidylcholine predicted cellular infiltration, infiltration type, elastosis, lymphatic invasion, perineural invasion, necrosis, and estrogen receptor positivity. (31)P MRS phospholipid profile data provide statistical correlations among histologic features and molecules known to play important roles in cellular communication, regulation, and processes unique to malignant tissues.