Human lung mast cell heterogeneity

Mast cells are found throughout the human body, both at mucosal surfaces and in the connective tissue of all organs. In fact, they are present in all classes of vertebrates including amphibians, reptiles, birds and mammals, and it has been estimated that the storage of histamine in vertebrate mast cells and its use as an inflammatory mediator was established in primitive reptiles (Lepidosauria) about 276 million years ago.1 This suggests that they mediate functions essential for life rather than representing a vestigial remnant of the immune system. Indeed, mast cells have been implicated in the regulation of many diverse homeostatic and pathological processes. For example, potential beneficial activities include defence against microbial infection with activation of both innate and acquired arms of the immune system, resistance to the effects of toxic venoms and roles in wound healing.2 3 Conversely, they are implicated in the pathophysiology of many diverse diseases such as atherosclerosis,4 allergy and asthma,5 pulmonary fibrosis6 and rheumatoid arthritis.7

Mast cells are able to achieve these diverse tissue effects through the release of numerous vasoactive and bronchospastic autacoid mediators (histamine, leukotriene C4 (LTC4), prostaglandin D₂ (PGD₂), serine proteases (tryptase, chymase), cytokines and chemokines.2 The release of these mediators is not “all-or-nothing”, but the pattern of molecules released is often tailored to the tissue insult. For example, using gene arrays, Okumura and colleagues showed that activation of cord blood-derived mast cells with anti-IgE, lipopolysaccharide (LPS), LPS + interferon γ (IFNγ) or IFNγ alone induced both core responses but also stimulus-specific responses.8 Furthermore, activation by LPS, for example, is able to induce cytokine secretion but not degranulation.9 It therefore seems likely that the normal role for the mast cell is to sense its external environment, ready to respond early to …