Correlation of the topographical arrangement and the functional pattern of tissue-infiltrating macrophages in giant cell arteritis

Cornelia M. Weyand, Annette D. Wagner, Johannes Björnsson, Jörg J. Goronzy

Research output: Contribution to journalArticlepeer-review

134 Scopus citations

Abstract

End organ ischemia, fragmentation of elastic membranes, and aneurysm formation in patients with giant cell vasculitis results from an inflammation destroying the mural layers of large and medium sized arteries. Although the inflammatory infiltrate extends through all layers of the affected blood vessel, the most pronounced changes involve the intima and the internal elastic lamina. Analysis of the functional profile of tissue infiltrating CD68+ cells demonstrates that different subsets of macrophages can be distinguished. TGFβ1-expressing CD68+ cells coproduce IL-1β and IL-6, are negative for inducible nitric oxide synthase (iNOS), and exhibit a strong preference for localization in the adventitia. The adventitial homing of TGFβ1+ CD68+ cells places them in the vicinity of IFN-γ secreting CD4+ T cells which also accumulate in the exterior layer of the artery. Conversely, iNOS expressing CD68+ cells are negative for TGFβ and are almost exclusively found in the intimal layer of the inflamed artery. The intimal-medial junction is the preferred site for 72-kD collagenase expressing CD68+ cells. Thus, TGFβ1-producing macrophages colocalize with activated CD4+ T cells and home to an area of inflammation which is distant from the site of tissue damage but critical in regulating cellular influx, suggesting that TGFβ1 functions as a proinflammatory mediator in this disease. iNOS- and 72-kD collagenase-producing macrophages accumulate at the center of pathology implying a role of these products in tissue destruction. These data indicate that the microenvironment controls the topographical arrangement as well as the functional commitment of macrophages.

Original languageEnglish (US)
Pages (from-to)1642-1649
Number of pages8
JournalJournal of Clinical Investigation
Volume98
Issue number7
DOIs
StatePublished - Oct 1 1996

Keywords

  • macrophage differentiation
  • metalloproteinase
  • TGFβ1
  • vasculitis

ASJC Scopus subject areas

  • Medicine(all)

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