ANCA-associated vasculitis (AAV) comprises granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). While systemic vasculitis is a hallmark of all AAV, GPA is characterized by extravascular granulomatous inflammation, preferentially affecting the respiratory tract. The mechanisms underlying the emergence of neutrophilic microabscesses; the appearance of multinucleated giant cells; and subsequent granuloma formation, finally leading to scarred or destroyed tissue in GPA, are still incompletely understood. This review summarizes findings describing the presence and function of molecules and cells contributing to granulomatous inflammation in the respiratory tract and to renal inflammation observed in GPA. In addition, factors affecting or promoting the development of granulomatous inflammation such as microbial infections, the nasal microbiome, and the release of damage-associated molecular patterns (DAMP) are discussed. Further, on the basis of numerous results, we argue that, in situ, various ways of exposure linked with a high number of infiltrating proteinase 3 (PR3)- and myeloperoxidase (MPO)-expressing leukocytes lower the threshold for the presentation of an altered PR3 and possibly also of MPO, provoking the local development of ANCA autoimmune responses, aided by the formation of ectopic lymphoid structures. Although extravascular granulomatous inflammation is unique to GPA, similar molecular and cellular patterns can be found in both the respiratory tract and kidney tissue of GPA and MPA patients; for example, the antimicrobial peptide LL37, CD163+ macrophages, or regulatory T cells. Therefore, we postulate that granulomatous inflammation in GPA or PR3-AAV is intertwined with autoimmune and destructive mechanisms also seen at other sites.

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Ciprofloxacin (200 mg) was infused to seven patients at the beginning of elective colorectal surgery. Thirty minutes after the end of infusion (i.e. 60 min after the start of the operation) ciprofloxacin reached concentrations of 1.60 mg/l in serum and of 3.42-6.07 mg/kg fresh weight in the ileum and colon. During the next 30 min (90 min after the start of operation) the concentration of ciprofloxacin in serum decreased to 86% of its initial level, but this decrease was less rapid than that observed in the ileal (to 56.8%) or colonic (to 74.8%) mucosa. Three metabolites could be identified (desethylen-, sulpho-, oxociprofloxacin). Initially, at 60 min the amount of these metabolites was about 15% of the total drug concentration in serum, but only 2-3% of that in the gut tissues. At 90 min the relative amount of metabolites was increased in serum as well as in the gut tissues. It is concluded that transintestinal elimination of ciprofloxacin is a general feature of the whole gut. Obviously, the elimination process is not due to degradation of ciprofloxacin within the gut wall.