title: Translocation of the neutrophil kinin moiety and changes in the regulation of kinin receptors in inflammation.
abstract: A molecular response to cell injury is the formation of chemotactic mediators that attract neutrophils to sites of inflammation. The question whether neutrophils contribute to circulating levels of kinins was examined in infections and inflammatory disorders. This novel hypothesis was tested using circulating neutrophils harvested from patients with tuberculosis meningitis and pneumonia. These neutrophils showed a distinct loss of only the kinin moiety from the kininogen located on the external surface. A similar loss of the kinin peptide was observed on the synovial fluid neutrophils obtained from the swollen, inflamed joints of patients with rheumatoid arthritis. The intriguing question is whether the circulating neutrophils simply reflect those cells re-entering the circulation from sites of inflammation. Anti-peptide antibodies to the peptide loops of cloned B1 and B2 receptors have provided a powerful probe for the cellular identification of the two kinin receptor families. We report the first localisation of B1 receptors on the basement membranes of bronchopulmonary cells and the surrounding fibrous stroma in transbronchial biopsies taken from patients with interstitial lung disease associated with progressive systemic sclerosis. Although binding of labelled bradykinin to neuronal membranes has been demonstrated, this is the first conclusive evidence for the presence of B1 kinin receptors in the neurons of human hypothalamus, caudate nucleus and the substancia gelatinosa of the spinal cord. Mapping of the B2 receptors in human tissues shows upregulation on the neutrophils gathered from inflamed joints, and absence from cell membranes of acutely rejecting transplant kidney. In addition, B2 receptors have also been demonstrated in neurons of the brain hypothalamus, caudate nucleus and cerebral cortex. Kinin receptor localisations in human tissue has considerable therapeutic implications.
authors.affiliation: Department of Experimental and Clinical Pharmacology, Natal Medical School, Durban, South Africa.
authors.forename: K D
authors.initials: KD
authors.lastname: Bhoola
mesh_terms: D001921:Brain / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007705:Kinins / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D011014:Pneumonia / Q000378:metabolism; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism*
chemical_list: D018836:Inflammation Mediators; D007705:Kinins; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D018000:Receptors, Peptide