melitten and Anaphylaxis

Episodic hemorrhage is not a typical symptom of anaphylactic reaction to insect stings. Cases of reactions to honeybee (HB) sting or venom immunotherapy in which the uterus is the main target organ are very rare. Hemorrhage can be induced by HB venom components, especially melittin, which interfere with complement cleavage and bradykinin release. Both mechanisms are directly or indirectly associated with coagulation, thrombolysis, hemolysis, and smooth muscle tone. Induction of episodic hemorrhage through pathway destabilization in a defective bradykinin system or vulnerable organ may not be compensated by appropriate regulatory mechanisms. The pathological role of effectors is generally offset by the interaction of various regulatory systems, and the probability of hemorrhage is minimized thanks to this compensatory capability. In endometrial bleeding, the uterus becomes more vulnerable as a result of postmenstrual vascular fragility and additional induction of anaphylaxis-related uterine contractions. Episodic hemorrhage, especially metrorrhagia, as a consequence of HB venom activity may be suspected by an allergologist, but not by a physician. Melittin-free or recombinant allergens of HB venom, as well as modulators of the biochemical systems involved, could help to reduce the likelihood of hemorrhage. However, further investigation is required before these strategies can be introduced in clinical practice.

Topics: Anaphylaxis; Animals; Bee Venoms; Bees; Bites and Stings; Bradykinin; Complement System Proteins; Female; Humans; Insect Bites and Stings; Melitten; Metrorrhagia; Uterus

Venoms consist of toxic components that are delivered to their victims via bites or stings. Venoms also represent a major class of allergens in humans. Phospholipase A2 (PLA2) is a conserved component of venoms from multiple species and is the major allergen in bee venom. Here we examined how bee venom PLA2 is sensed by the innate immune system and induces a type 2 immune response in mice. We found that bee venom PLA2 induced a T helper type 2 (Th2) cell-type response and group 2 innate lymphoid cell activation via the enzymatic cleavage of membrane phospholipids and release of interleukin-33. Furthermore, we showed that the IgE response to PLA2 could protect mice from future challenge with a near-lethal dose of PLA2. These data suggest that the innate immune system can detect the activity of a conserved component of venoms and induce a protective immune response against a venom toxin.

Topics: Anaphylaxis; Animals; Bee Venoms; Crotalid Venoms; Genes, Reporter; Immunity, Innate; Immunoglobulin E; Immunoglobulin G; Insect Proteins; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Interleukin-4; Interleukins; Lymphocyte Activation; Lysophospholipids; Melitten; Membrane Lipids; Mice; Mice, Inbred BALB C; Mice, Knockout; Myeloid Differentiation Factor 88; Ovalbumin; Phospholipases A2; Phospholipids; Receptors, IgE; Receptors, Interleukin; Th2 Cells

To determine the rate and completeness of delivery of venom from honeybee stings, European bees were collected at the entrance of a hive and studied with the use of two laboratory models. In one model bees were induced to sting the shaved skin of anesthetized rabbits. The stings were removed from the skin at various time intervals after autotomization, and residual venom was assayed with a hemolytic method. In the other model the bees were induced to sting preweighed filter paper disks, which were weighed again after removal of the sting at various intervals. Results of both experiments were in agreement, showing that at least 90% of the venom sac contents were delivered within 20 seconds and that venom delivery was complete within 1 minute. The data suggest that a bee sting must be removed within a few seconds after autotomization to prevent anaphylaxis in an allergic person. The extensive variation found in the amount of venom delivered at each time point may explain inconsistencies in relationships among reactions to field stings, sting challenge testing, venom skin tests and RAST.

Topics: Anaphylaxis; Animals; Bee Venoms; Bees; Insect Bites and Stings; Melitten; Rabbits; Skin; Time Factors