Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The adherence of Bordetella pertussis to human respiratory cilia is critical to the pathogenesis of whooping cough but the significance of bacterial attachment to macrophages has not been determined. Adherence to cilia and macrophages is mediated by two large, nonfimbrial bacterial proteins, filamentous hemagglutinin (FHA), and pertussis toxin (PT). PT and FHA both recognize carbohydrates on cilia and macrophages; FHA also contains an Arg-Gly-Asp (RGD) sequence which promotes bacterial association with the macrophage integrin complement receptor 3 (CR3). We determined that virulent B. pertussis enter and survive in mammalian macrophages in vitro and that CR3 is important for this uptake process. We then determined the relative contribution of CR3 versus carbohydrate-dependent interactions to in vivo pulmonary colonization using a rabbit model. B. pertussis colonized the lung as two approximately equal populations, one extracellular population attached to ciliary and macrophage surface glycoconjugates and another population within pulmonary macrophages. Loss of the CR3 interaction, either by mutation of FHA or treatment with antibody to CR3, disrupted accumulation of viable intracellular bacteria but did not prevent lung pathology. In contrast, elimination of carbohydrate-bound bacteria, either by a competitive receptor analogue or an anti-receptor antibody, was sufficient to prevent pulmonary edema. We propose that CR3-dependent localization of B. pertussis within macrophages promotes persistence of bacteria in the lung without pulmonary injury. On the other hand, the presence of extracellular bacteria adherent to cilia and macrophages in carbohydrate-dependent interactions is associated with pulmonary pathology.
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PMID:Integrin-mediated localization of Bordetella pertussis within macrophages: role in pulmonary colonization. 202 24

This case highlights the difficulties associated with the differential diagnosis of pulmonary symptoms in patients with pre-existing diseases in extreme environmental conditions. A 58-year-old man with child-onset allergic asthma developed dyspnoea and an acute non-productive cough during a trekking expedition on Mt. Kilimanjaro (5895m) in Tanzania. The symptoms were believed initially to be linked to the high altitude exposure (high altitude pulmonary oedema (HAPE) or high altitude cough) or his pre-existing asthma. However, he was later diagnosed correctly with a reinfection of Bordetella pertussis. Pertussis is a highly communicable disease with potentially serious medical consequences that could have affected all of the expedition members. The effectiveness of a pertussis vaccine declines 4-12 years after the vaccination. Thus, it is suggested that the status of immunisation against pertussis should be checked along with those of other infections prior to travel.
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PMID:Cough and dyspnoea of an asthmatic patient at Mt. Kilimanjaro: a difficult differential diagnosis. 2018 1