The Acari Hypothesis, III: Atopic Dermatitis.

Atopic dermatitis is a chronic relapsing dermatopathology involving IgE against allergenic materials present on mammalian epithelial surfaces. Allergens are as diverse as pet danders, and polypeptides expressed by microbes of the mammalian microbiome, e.g., Malassezia spp. The Acari Hypothesis posits that the mammalian innate immune system utilizes pathogen-bound acarian immune effectors to protect against the vectorial threat posed by mites and ticks. Per The Hypothesis, IgE-mediated allergic disease is a specious consequence of the pairing of acarian gastrointestinal materials, e.g., allergenic foodstuffs, with acarian innate immune effectors that have interspecies operability. In keeping with The Hypothesis, the IgE profile of atopic patients should include both anti-acarian antibodies and specious antibodies responsible for specific allergy. Further, the profile should inform on the diet and/or environment of the acarian vector. In this regard, the prevalence of Demodex and Dermatophagoides on the skin of persons suffering from atopic dermatitis is increased. Importantly, the diets of these mites correspond well with the allergens of affected patients. In this report, roles for these specific acarians in the pathogenesis of atopic dermatitis are proposed and elaborated.

Competing Bioaerosols May Influence the Seasonality of Influenza-Like Illnesses, including COVID-19. The Chicago Experience.

Data from Chicago confirm the end of flu season coincides with the beginning of pollen season. More importantly, the end of flu season also coincides with onset of seasonal aerosolization of mold spores. Overall, the data suggest bioaerosols, especially mold spores, compete with viruses for a shared receptor, with the periodicity of influenza-like illnesses, including COVID-19, a consequence of seasonal factors that influence aerosolization of competing species.

The Acari Hypothesis, II: Interspecies Operability of Pattern Recognition Receptors.

Hypersensitivity to galactose-α-1,3-galactose (α-gal) is an informative example of a pathologic IgE-mediated process. By way of their saliva, ticks are able to sensitize humans to tick dietary elements that express α-gal. Mites, which along with ticks constitute the phyletic subclass Acari, feed on proteinaceous foodstuffs that represent most, if not all, human allergens. Given: (1) the gross nature of the pathophysiological reactions of allergy, especially anaphylaxis, (2) the allergenicity of acarian foodstuffs, and (3) the relatedness of ticks and mites, it has been hypothesized that human-acarian interactions are cardinal to the pathogenesis of allergy. In this report, a means by which such interactions contribute to that pathogenesis is proposed.

Mites, ticks, anaphylaxis and allergy: The Acari hypothesis.

Anaphylaxis is a poorly understood immune process in which a Th2-/IgE-mediated adaptive response commandeers cellular machinery, typically reserved for defense against multicellular ectoparasites, to activate against otherwise benign molecules. Its clinical manifestations consist of rapid pathophysiological reflexes that target epithelial surfaces. The galactose-α-1,3-galactose hypersensitivity response is a compelling model of anaphylaxis for which causation has been demonstrated. At the core of the model, a tick bite sensitizes a recipient to a tick foodstuff. As proposed herein, the model likely informs on the origin of all allergic inflammation; namely, allergy is not intended to protect against seemingly harmless and irrelevant materials, but is, instead, intended to rid epithelial surfaces of pathogen-bearing Acari, i.e., mites and ticks. The demonstrated adjuvant activity of acarian gastrointestinal secretions, when paired with the polyphagous diet of mites, renders acarians eminently suited to accounting, mechanistically, for many, if not all, human allergies.

Extracellular transport of cell-size particles and tumor cells by dendritic cells in culture.

Many particulate materials of sizes approximating that of a cell disseminate after being introduced into the body. While some move about within phagocytic inflammatory cells, others appear to move about outside of, but in contact with, such cells. In this report, we provide unequivocal photomicroscopic evidence that cultured, mature, human dendritic cells can transport in extracellular fashion over significant distances both polymeric beads and tumor cells. At least in the case of polymeric beads, both fibrinogen and the ß2-integrin subunit, CD18, appear to play important roles in the transport process. These discoveries may yield insight into a host of disease-related phenomena, including and especially tumor cell invasion and metastasis.

A turbidimetric method for measuring the activity of trypsin and its inhibition.

Microscopic poly(styrene-divinylbenzene) beads coated with a monomolecular film of fibrinogen agglutinate when stirred in the presence of thrombin, a consequence of interbead fibrin formation. Trypsin, by digesting bead-bound fibrin, dissociates bead aggregates at a rate proportional to the amount of enzyme activity. The agglutination of beads and the dissociation of bead aggregates can be monitored turbidimetrically using a platelet aggregometer or other photometric device equipped with a stirred cell. We have exploited the behavior of aggregates of fibrin-coated beads to develop a rapid, sensitive, and accurate method for measuring the activity of trypsin and its inhibition, in aqueous media, including serum. The new method yields serum antitrypsin activity levels that correlate well with immunological levels of alpha1-antitrypsin and, thus, may prove useful for assessing antitrypsin activity in clinical specimens.

Fibrinogen-coated droplets of olive oil for delivery of docetaxel to a fibrin(ogen)-rich ascites form of a murine mammary tumor.

Micronized droplets of olive oil loaded with docetaxel and coated with functional fibrinogen were administered intraperitoneally to mice bearing the fibrin(ogen)-rich ascites form of the TA3/St mammary tumor. When compared with docetaxel administered intraperitoneally as its commercial formulation (i.e., Taxotere), docetaxel-loaded oil droplets coated with murine fibrinogen prolonged the median survival time of tumor-bearing mice from 14.5 to 29.5 days. Drug-free oil droplets provided no therapeutic benefit. Significantly more docetaxel was associated with tumor cells 24 and 48 hours after administration of the drug in fibrinogen-coated oil droplets than after its administration as Taxotere. Consistent with a role for thrombin in the retention of fibrinogen-coated oil droplets within the tumor microenvironment, hirudin significantly reduced the association of tumor cells with docetaxel delivered in fibrinogen-coated oil droplets and, at the same time, reduced the therapeutic efficacy of the droplets to that of Taxotere. Importantly, fibrinogen-coated oil droplets formed rosettes with tumor cells in vivo, a process prevented by hirudin. Although mice treated with oil droplets developed antifibrinogen antibodies, those antibodies seemed to be inconsequential. Taken together, our results and observations indicate fibrinogen-coated oil droplets markedly improve the therapeutic efficacy of docetaxel for the treatment of a mammary tumor grown in ascites form, a consequence of thrombin-mediated retention of the drug-loaded droplets within the tumor microenvironment.