Two subsets of circulating Ly6Clo monocytes distinguished by CD138 (syndecan-1) expression and Nr4a1 dependence in pristane-treated mice

Chronic peritoneal inflammation following pristane injection induces lupus with diffuse alveolar hemorrhage (DAH) and pulmonary capillaritis in C57BL/6 mice. The pathogenesis involves pristane-induced microvascular lung injury. BALB/c mice are resistant to endothelial injury and DAH. Lung disease in C57BL/6 mice is abolished by depleting monocytes/macrophages. The objective of this study was to define the role of myeloid subsets in DAH. Hemorrhage and vasculitis were abolished in Ccr2-/- mice, indicating involvement of bone marrow-derived monocytes/macrophages. Along with Ly6Chi monocytes, we found two subsets of circulating Ly6Clo monocytes: one CD138- and a novel CD138+ subset. Nr4a1-dependent patrolling Ly6Clo monocytes maintain vascular integrity after endothelial injury. Circulating Ly6CloCD138+ monocytes were associated with DAH and were absent in mice without DAH. They also were absent in Nr4a1-/- mice, whereas Ly6CloCD138- monocytes were unaffected. However, Nr4a1-/- mice were susceptible to pristane-induced DAH and lung vasculitis, suggesting that disease onset does not require Ly6CloCD138- monocytes. Peritoneal Ly6CloCD138+ M? were unchanged in Nr4a1-/- mice, indicating that they are not derived from Ly6CloCD138+ monocytes. We conclude that pristane-induced lung microvascular lung injury stimulates a wave of Nr4h1-dependent Ly6CloCD138+ patrolling monocytes in an ineffectual effort to maintain vascular integrity in the face of ongoing endothelial damage.

Microscopic polyangiitis: Modern concepts and treatment options

The article summarizes the modern concepts of microscopic polyangiitis (MPA), a primary ANCA-associated systemic necrotizing vasculitis without immune globulin deposition (pauci-immune) that affects mainly small vessels, while granulomatous inflammation is absent. Necrotizing glomerulonephritis is very common and pulmonary capillaritis often occurs. MPA can cause rapidly progressive damage to organ systems. The modern possibilities of MPA treatment, primarily anti-B cell therapy with rituximab, are discussed.

Pulmonary Capillaritis: The Breakdown of the Histologic Features

Introduction/Objective Capillary inflammation (capillaritis) is rarely the primary pathologic cause of pulmonary hemorrhage. It may coexist with vasculitis. The aim of this study is to investigate the specificity of five histologic features of pulmonary capillaritis previously described by Mark and Ramirez (discussed below). They are usually treated with corticosteroids and cyclophosphamide or azathioprine. Methods A retrospective review of patients with a pathologic diagnosis of capillaritis in open lung biopsies was done. The diagnosis was confirmed by two expert pulmonary pathologists. The slides were reviewed and compared to a control group, who also underwent open lung biopsies for clinical suggestion of pulmonary hemorrhage and no pathologic diagnosis of capillaritis. Cases with malignant neoplasms, large and medium size vasculitis syndromes, and diffuse alveolar damage (DAD) were excluded. The five pathologic features of capillaritis were evaluated and scored as negative (0), focal (1+) and moderate to diffuse (2+) in both groups. Results Five cases of pulmonary capillaritis and five cases in control group were identified. The etiology of pulmonary capillaritis in the five identified cases included autoimmune diseases, pulmonary hypertension, non-specific interstitial pneumonia, and idiopathic capillaritis. The average score for the morphologic features of capillaritis versus the control group were as follows: Interstitial erythrocytes and/or hemosiderin (2+ vs 2+), fibrinoid necrosis of capillary walls (2+vs 0), intraalveolar septal capillary occlusion by fibrin thrombi (1+ vs 0), neutrophils and nuclear dust in the interstitium, in the fibrin, and in the adjacent alveolar spaces (2+ vs 1+), and fibrin clots attached to interalveolar septa in a sessile manner (2+ vs 1+). Conclusion In this small study, we can conclude that fibrinous necrosis is the most specific finding for pulmonary capillaritis while interstitial erythrocytes and/or hemosiderin is least specific. Therefore, in the presence of fibrinous necrosis; in addition to other supporting features; a pathologist is more inclined to communicate a diagnosis of pulmonary capillaritis to the clinicians.