Histamine is found in abundance in mast cells, which are normally present in connective tissues next to blood vessels beneath mucosal surfaces in airways. Binding of an antigen (allergen) to IgE antibodies that have previously attached to the mast cells by the Fc receptor triggers mast cell degranulation, with release of histamine. This response causes increased vascular permeability and mucous secretions. Bradykinin, generated from the kinin system on surface contact of Hageman factor with collagen and basement membrane from vascular injury, promotes vascular permeability, smooth muscle contraction, and pain. Complement C5a is a potent chemotactic factor for neutrophils. Interleukin-1 (IL-1) and tumor necrosis factor (TNF), both produced by activated macrophages, mediate many systemic effects, including fever, metabolic wasting, and hypotension. Phospholipase C, which catalyzes the release of arachidonic acid, is generated from platelet activation.